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West Yorkshire Comprehensive Local Research Network
BRADFORD TEACHING HOSPITALS NHS TRUST
West Yorkshire Research
Induction Pack
for Nurses, Midwives and other
Allied Health Professionals
Name .........................................................................................................
Job Title .....................................................................................................
Department ................................................................................................
Start Date ..................................................................................................
Line Manager ............................................................................................
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CONTENTS ▼ = denotes local Trust information
Introduction▼
Research & the NHS
National Institute of Health Research and the Networks ▼
Trust R&I Strategy ▼
Research Governance
Declaration of Helsinki
EU Directives, Statutory Instruments and MHRA
Good Clinical Practice
Health Research Authority & Ethics
Roles & Responsibilities of Researchers & Organisations
Amendments
Safety
Human Tissue Act
Data Protection
Informed Consent
SOPs Standard Operating Procedures training log ▼
Clinical Research Nurse Induction programme
Local research induction
Induction Programme line manager sign off
Trial design
Case Report Forms
Essential Documents
Clinical Research Nurse Competency Tool
Appendices
I Clinical Research Forum Terms of References ▼ II Training Folder Template III Research CV template IV Glossary and Further Resources V Useful contacts ▼
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Acknowledgements:
The following were members of the Clinical Research Induction Working Group:
Angela Grange
Emma Giddings
Sue Williamson
Clive Nicholson
Heather Rostron
Victoria Drew
Linda Bamford
This document has been based on Leeds Teaching Hospitals NHS Trust Clinical Research
Nurse Induction Pack & Competency Framework and Yorkshire Cancer Research
Network’s Induction Handbook.
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Introduction
Welcome to the Bradford Institute for Health Research
The Bradford Institute for Health Research was established in 2007 as a unique research partnership between the primary and secondary care NHS Trusts in Bradford and Airedale and the universities of Bradford, Leeds and York. There is a real passion and commitment from the partners of the BIHR to harness the potential for expanding research in Bradford and establish the Bradford NHS community as a national leader in applied health research.
The BIHR has developed a strong track record in applied research and is a national centre of excellence in
a number of health priority areas. It provides a physical centre for academic and research staff
employed by the Trust as well as the Universities of Leeds and Bradford, and houses a number of these
staff.
Whatever your previous roles and experience, you will bring with you a variety of knowledge and skills. However, coming into the world of clinical research from hands-on care provision involves the development of new and different clinical skills, which is both exciting and challenging. As well as keeping your existing skills, additionally you will learn many new ones We hope you will find that the role of clinical research nurse is varied and interesting - everyday is different from the one before. Research nurses take part in a study from start to finish (they hear and learn about a completely new study, enrol patients and are there to see the results that will make a difference to the patient and their families in the future). Research nurses play a vital role in supporting patients throughout the course of the research, ensuring
clinical studies run smoothly and that participants are safe and fully informed. They may be responsible
for recruiting patients, gaining consent from patients to take part in a study, collecting data, carrying out
study-related clinical procedures and much more.
This booklet is designed to be a practical and informative resource to you. Take every opportunity to
obtain advice and support from your research colleagues and R&D Department.
Wishing you every success in your post,
Angela Grange
Lead Nursing Clinical Quality & Research/Trust Innovation Lead
Emma Giddings,
Lead Nurse WYCLRN
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RESEARCH AND THE NHS
Why engage in research
Studies suggest that patients who receive care in research-active institutions have better health
outcomes than patients who are treated in a non-research environment, so by joining the research
community you are actively helping to drive up the standard of healthcare for your patients. By
investigating the cause and course of diseases and how best to treat them, you are also helping to
establish ‘what works’ and build the body of evidence that can lead to a positive change in future care.
The importance of Research within the NHS
The Department of Health’s strategy to improve the health of the nation continues to place research at
the forefront of the NHS. The recent White Paper Equity and excellence: liberating the NHS (DH 2010)
highlights research in terms of quality, transparency and value for money, with the aim of achieving
health outcomes as good as anywhere else in the world. It aims to deliver quality care from evidence
based practice which is thoroughly researched. The NHS has a constant challenge to provide a service
that is up to date and efficient. Health research plays a key role in this service by using the evidence
from studies to support health strategies and changes in medical practice.
The NHS now has a thriving research culture that promotes fairness of access across England for patients
and health professionals to take part in multi-centre studies. As a member of a clinical research team
you will play a key role in contributing to this research culture through clinical trials and/or health
related research, therefore continually improving the quality and choices available for patients and
healthcare as a whole.
The Plan for Growth: http://cdn.hm-treasury.gov.uk/2011budget_growth.pdf
Liberating the NHS, Equity and Excellence:
http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH
_117353
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Supporting research to make patients, and the NHS, better
www.crncc.nihr.ac.uk
The NIHR Clinical Research Network (NIHR CRN) is part of the NIHR, specifically tasked with ensuring that
the infrastructure for research in the NHS enables studies to happen as quickly and efficiently as
possible including:
- Access to experienced Research Management and Governance staff who can advise on and
facilitate the governance aspects of undertaking clinical research in the NHS.
- Support to ensure studies can be successfully undertaken in the NHS.
In England, the Department of Health has determined that research studies (clinical trials and other well
designed studies which involve the NHS) that are funded by NIHR, other areas of Government and NIHR
non-commercial Partners are automatically eligible to be included in a database called the NIHR CRN
Portfolio (National Institute for Health Research Clinical Research Network Portfolio). In addition, other
studies, such as those that are commercially sponsored or those with industry funding that are led by a
local investigator, may be considered for inclusion in the NIHR CRN Portfolio by undergoing an adoption
process. ‘NIHR Portfolio studies’ have access to infrastructure support and funding for service support
costs via the NIHR.
Stu
dy p
lan
nin
g
•Advice on available facilities/ support staff
•Ideas on supporting clinicians
•Intelligence on local patient populations
Stu
dy s
et-
up
•Systems to reduce red-tape on multi-site studies
•Managing NHS R&D approval process
•Speeding up set-up times
Stu
dy d
elive
ry
•Funding of facilities and people to carry out research
•Recruiting patients into studies
•Providing training for research staff
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NIHR Infrastructure
Clinical Research Network
HQ
Comprehensive
(CCRN)
Cancer
(NCRN)
Diabetes
(DRN)
Dementia & neuro
(DeNDRoN)
Mental Health
(MHRN)
Medicines for
Children
(MCRN)
Primary Care
(PCRN)
Stroke
(SRN)
Topics Networks support research in the priority areas of Cancer, Diabetes,
Dementia & Neurodegenerative Diseases, Mental Health, Medicines for Children,
Stroke and Primary Care.
In addition to the topic specific research networks, the Comprehensive Clinical
Research Network (CCRN), comprising 25 Comprehensive Local Research
Networks, makes it possible for all patients and health professionals across
England to participate in clinical trials in all other areas of disease and clinical
need within the NHS.
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www.westyorks.crncc.nihr.ac.uk
“The West Yorkshire Comprehensive Local Research Network operates as part of the NIHR
Comprehensive Clinical Research Network in England. It is part of the National Institute for Health
Research and forms part of the UK Clinical Research Network. The Networks support and deliver high
quality clinical research studies.”
The role of West Yorkshire CLRN:
Provide support and signpost researchers during the planning, set up and delivery phase of a
study.
Research Management & Governance service through the Integrated Research Application
System (IRAS) and NIHR Co-ordinated System for gaining NHS Permission (NIHR CSP).
Support Local Specialty Groups to bring together researchers to provide a local focus for activity
in that disease area.
The NIHR CRN is committed to helping the life science industry deliver high quality research to
time and target in a well managed, efficient and cost effective environment. This is facilitated in
West Yorkshire through a dedicated industry manager, who provides a single point of contact for
all services.
2012/13 budget of £12.3m for West Yorkshire:
Service Support Costs
Clinical infrastructure (consenting patients/retrieving outcome data)
o Clinical sessions
o Research nurses
Key service support
o Pharmacy, Radiology, Pathology
o Translators, clinical trials coordinators, information managers
Research Capability Funding (RCF)
o Staff costs of researchers between portfolio grants
o Staff costs of researchers who haven’t yet obtained portfolio funding, but are expected
to imminently.
The WYCLRN provide funding for research posts across the region and the Lead Nurse role is to provide
leadership and support to this workforce. She can be contacted as below:
Emma Giddings, WYCLRN, 34 Hyde Terrace, Leeds, LS2 9LN. T 0113 392 3765 M 07534 274555 E [email protected]
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Yorkshire Cancer Research Network
The Yorkshire Cancer Research Network (YCRN) is 1 of 32 cancer networks across England which are co-ordinated by the National Institute for Health Research Cancer Research Network (NCRN). The NCRN is a part of the National Institute for Health Research (NIHR).
The NIHR supports and funds NHS research through the NCRN and five other Topic disease areas, a Primary Care Network and a Comprehensive Research Network ensuring all areas of research are covered.
The YCRN works closely with its two Comprehensive Local Research Networks – West Yorkshire and North & East Yorkshire & North Lincolnshire (WY CLRN & NEYNL CLRN). Additional CLRN funds supports the cancer clinical trials portfolio.
The YCRN is also part of the Yorkshire Cancer Network (YCN), which provides cancer care for a population of over 2.6 million people.
It embraces 7 acute hospitals:
Airedale NHS Foundation Trust Bradford Teaching Hospitals NHS Foundation
Trust Calderdale and Huddersfield NHS Foundation
Trust Harrogate and District NHS Foundation Trust Mid Yorkshire NHS Trust Leeds Teaching Hospitals NHS Trust York Teaching Hospitals NHS Foundation Trust
and several Primary Care Trusts (CCGs):
NHS Leeds North CCG
NHS Leeds West CCG
NHS Leeds South and East CCG
NHS Bradford City CCG
NHS Bradford Districts CCG
NHS Airedale, Wharfedale and Craven CCG
NHS Vale of York CCG
NHS Harrogate and Rural CCG
NHS Calderdale CCG
NHS Greater Huddersfield CCG
NHS North Kirklees CCG
NHS Wakefield CCG
What we do
The YCRN supports and funds research staff across the YCN to work on a large number of cancer clinical trials. The YCRN aims to:
Create a balanced and equitable local cancer clinical trial portfolio focusing on local Trust strengths ensuring NIHR recruitment targets are met.
Ensure timely and efficient clinical trial setup for network Trusts and improve the integration of these trials into clinical practice, ultimately resulting in improved patient care.
Raise research awareness in healthcare professional and service users groups Encourage patient and public involvement in the development of cancer clinical trials Provide and facilitate a comprehensive training and education programme
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Yorkshire Stroke Research Network
Yorkshire, North Yorkshire, East Yorkshire and North Lincolnshire (Scunthorpe and Goole)
The Yorkshire Stroke Research Network aims to improve the speed, quality, and integration of research,
ultimately resulting in improved patient care. We provide structures and support to local clinicians to get
involved in recruiting patients to high quality multicentre trials.
In 2012 the YSRN was named "Local Research Network of the Year" at the national SRN conference.
How the Network Works
We aim to provide a first class environment for stroke research and improve the care of people with
stroke and their carers. The YSRN operates through maximising autonomy for local clinicians. The
network provides the staff with training, advice, opportunities and resources to set-up and manage
trials, but clinicians decide which trials to run, based on their expert knowledge of local conditions,
interests and potential. Possible projects are discussed and presented at regular network meetings and
then quickly rolled out across an informed network.
Most of the resources of the network are devolved to local sites in the form of high-quality research
staff. These researchers are performance managed from the centre, but embedded in the local clinical
team.
The YSRN is proud to be a genuinely open network. YSRN network meetings are held jointly with the
West Yorkshire Stroke Group, the established clinical network, and are open to all. We have a broad
cross-section of people with an interest in stroke and stroke research on our Management, Executive
and Research Advisory (patient and carer) groups who are all consulted about our work and plans.
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Stroke Research Sites in the YSRN
The YSRN works mainly in stroke units in acute hospitals, but we also collaborate with other organisations to conduct research in, for example, primary care. We have staff based in the following organisations: Airedale NHS Trust
• Airedale General Hospital
Bradford Teaching Hospitals NHS Foundation
Trust
• Bradford Royal Infirmary
• St Luke’s Hospital
Calderdale & Huddersfield NHS Trust
• Calderdale Royal Hospital
• Huddersfield Royal Hospital
Harrogate and District NHS Foundation Trust
• Harrogate District Hospital
Hull and East Yorkshire NHS Foundation Trust
• Hull Royal Infirmary
• Castle Hill Hospital
• The Princess Royal Hospital
Leeds Teaching Hospitals NHS Trust
• Leeds General Infirmary
• St James’s University Hospital
• Chapel Allerton Hospital
Mid Yorkshire Hospitals NHS Trust
• Dewsbury and District Hospital
• Pinderfields General Hospital
• Pontefract General Infirmary
Northern Lincolnshire and Goole Hospitals NHS
Foundation Trust
• Diana, Princess of Wales Hospital, Grimsby
• Goole and District Hospital
• Scunthorpe General Hospital
Scarborough and North East Yorkshire Health Care
NHS Trust
• Scarborough General Hospital
York Hospitals NHS Foundation Trust
• York Hospital
The YSRN is Hosted by Bradford Teaching Hospitals NHS Foundation trust. For more information
contact:
Stephen Lock, YSRN Manager Yorkshire Stroke Research Network Bradford Institute for Health Research Temple Bank House Bradford Royal Infirmary Duckworth Lane Bradford BD9 6RJ T: 01274 383 425 F: 01274 382 768
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West Yorkshire research for CHildren
The West Yorkshire research for CHildren (WYCH) aims to develop research capacity using experience
from Greater Manchester Lancashire and south Cumbria MCRN (GMLC) to help local NHS staff and their
organisations to create a sustainable infrastructure to support paediatric research.
The West Yorkshire Comprehensive Local Research Network (WY CLRN) provided significant funding to
support new research nurses and medical time in all hospital Trusts in the area with recruitment
extending into primary care and the community for some studies.
WYCH supports National Institute for Health Research (NIHR) portfolio studies that fall under either
MCRN or Paediatric Specialty Group (PSG). Current MCRN and PSG portfolio studies can be found at the
NIHR CRN Clinical Research Portfolio webpage.
The WYCH team works closely with the GMLC team helping local clinical staff successfully set up and
deliver MCRN and PSG studies. The recruitment phase and other aspects of the study management
process are managed locally by the WYCH team.
The team:
11 Research Nurses and 1 Senior Research Nurse work across West Yorkshire, with nursing hubs in
Bradford and Leeds. Research Leads drive and champion paediatric research in all West Yorkshire District
General Hospitals and also in the speciality of neonatology. Most of the WYCH team are featured in the
photograph below.
Dr Tim Lee (far right) is a Consultant Paediatrician based at Leeds General Infirmary and is the West
Yorkshire MCRN lead. Heather Rostron (front 2nd right) is the West Yorkshire MCRN Senior Research
Nurse. The Leeds nurse team is led by paediatric oncology Senior Research Nurse Linda Phelan (5th right
back row) with Research Nurses: Becky Mottram (2nd right back row); Majorie Allen (3rd right front
row); Nicky Balatoni (4th left top row) and Jane Exall (3rd right top row). We also support Annabel Nixon
(2nd left top row) who is funded to work on an MCRN adopted Marfans Syndrome study. Our Bradford
hub comprises of Research Nurses Louise Akeroyd (front left) and Kelly Young (6th left top row) and we
have part time nurses based at Airedale Hospitals Trust; Mandy Swanepoel (5th left top row), Calderdale
and Huddersfield Hospitals Trust; Rachel Swingler (2nd left bottom row) and at Mid Yorkshire Hospitals
Trust; Gail Castle (4th right bottom row). Also, Sarah Rickard is our GMLC-MCRN Network Manager
(bottom right), and our WYCH Administrator is Stephanie Hill (3rd left top row).
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Contact us:
Heather Rostron; 0777 209 2410
Airedale
Dr Pronab Bala ([email protected])
Mandy Swanepoel ([email protected]) 01535 293934
Bradford
WYCH Office - 01274 382318
Louise Akeroyd ([email protected])
Kelly Young (Kelly.Young2@ bthft.nhs.uk)
Calderdale & Huddersfield
Rachel Swingler ([email protected]) 077668 20793
Dr Lynne Terrett - 01484 342361
Leeds
WYCH Office – 0113 392 3995
Dr Tim Lee ([email protected])
Majorie Allen ([email protected])
Becky Mottram ([email protected])
Darren Hewett ([email protected])
Jane Exall ([email protected])
Gill Jackson ([email protected])
Mid Yorkshire
Dr Kath Deakin ([email protected])
Gail Castle ([email protected]) 01924 543778
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▼Bradford Institute for Health Research
The BIHR has a particular focus on public health research, with major programmes including:
Born in Bradford – one of the world’s largest public health research projects following the lives of 10,000 families in the city.
Stroke and elderly care – hosting the regional stroke research network and one of the leading centres for elderly care research in the UK.
Patient safety – developing innovative solutions to improve the major public health issue of patient safety
Maternal and child health – a new centre covering obstetric trials, paediatric epidemiology and childhood obesity.
The BIHR has developed a strong track record in applied research and is a national centre of excellence in a number of health priority areas. In 2006 Bradford became the only centre in Yorkshire to win a clinical research network application with the £2 million Yorkshire Stroke Network.
During 2007-09 researchers in Bradford were successful in winning major National Institute for Health Research (NIHR) programme grants worth £5 million for:
rehabilitation, child health, delirium patient safety and a developmental programme grant in Quality and Safety
The BIHR also hosts the Born in Bradford research programme which has been successful in winning over £7 million in research grants over the last two years.
The Institute provides a physical centre for academic and research staff employed by the Trust and the
Universities of Leeds and Bradford and houses a number of these staff. In addition it provides the
following facilities for health care professionals in the Trusts:
1. Purpose-designed clinical research facility for all patients involved in commercial and non-commercial clinical trials, supported by high calibre, dedicated research nurses
The Bradford Institute for Health Research was established in 2007 as a unique research partnership between the primary and secondary care NHS Trusts in Bradford and Airedale and the universities of Bradford, Leeds and York. There is a real passion and commitment from the partners of the BIHR to harnessing the potential for expanding research in Bradford and establish the Bradford NHS community as a national leader in applied health research.
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2. A hub for all clinical researchers in Bradford across all disciplines. 3. An Exchange area where researchers can meet and network and share their research ideas and
expertise. 4. A formal meeting room for research training and research meetings and seminars 5. A Research Design Service for supporting grant development for clinical staff with new ideas.
The vision for the Bradford Institute for Health Research is to become a national centre for excellence in health research and to forge a unique research collaboration between the people of Bradford, the NHS community and the Universities of Leeds and Bradford. A strategy for the BIHR has been produced which details its strategic aims and objectives for the next five years. To summarise, its aims are:
To develop high quality research capacity across the Bradford research community. To undertake research programmes that will translate into real benefits for patients. To provide an opportunity for local people to share the benefits of participation and involvement
in healthcare research. To develop and attract the best researchers. To ensure high standards for research governance and minimise bureaucracy.
There will also be a number of activities that will be undertaken by the Institute:
Research governance support – the Bradford Teaching Hospitals NHS Foundation Trust’s Research Support and Governance Office is housed within the Institute and provides the full spectrum of research advice and support to researchers including advice on data protection, research passports and honorary contracts, approval processes and applications and quality assurance.
Research advice - methodological support and identification of grant opportunities Training and research events for researchers - research training is provided on subjects such as
research governance and GCP training but the Institute also hosts regular research meetings where staff can present their research. This latter activity not only encourages collaborations but will enable staff to learn about each other´s research activity.
Information to patients and public – within the Clinical Research Facility there is information resources for the patients and the public about research in the Trust and what they can expect if they get involved in a research project.
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Research Governance
All health and social care research arrived out in the UK is governed by strict regulations. They exist to
ensure that research is carried out consistently to high ethical and scientific standards, and to prevent
performance, adverse events where possible, research misconduct and fraud. They also help to ensure
that lessons are learned and shared when poor practice is identified. Organisations involved in clinical
research have a duty to foster a high quality research culture and individuals have a duty to ensure that
they, and those they manage, are appropriately qualified by training, education and experience for the
roles that they undertake.
Research Governance Framework
Research Governance Framework for Health and Social Care, 2001 (updated 2005) was published by
Department of Health (DH) to provide a practical framework for the governance of research in health
and social care in the UK. It applies to everybody involved in research (clinical and non-clinical)
undertaken by NHS staff using NHS resources. This includes research undertaken by industry, charities,
research councils and universities within the health and social care systems. The rules apply to
researchers, managers and staff in all professional groups, no matter how senior or junior, as well as to
research participants.
Research Governance Framework
Any research within the responsibilities of the Secretary of State for Health,
including any research conducted in the NHS in England.
CTIMPs and Non-CTIMPs
CTIMPs are also governed by UK Medicines for Human Use (Clinical Trials) Regulations
and overseen by the UK Competent Authority, the Medicines and Healthcare
Regulatory Agency (MHRA)
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The RGF outlines the key roles and responsibilities of both researchers and organisations that are
accountable for the proper conduct of a study. It requires that formal agreements are in place
describing the allocation of these responsibilities. Below are summaries of these roles and
responsibilities and a brief outline of how these are applied in practice.
Research Governance:
Sets standards
Defines mechanisms to deliver standards
Describes monitoring and assessments arrangements
Research Governance improves research quality and safeguards the public by:
Enhancing ethical and scientific quality
Promoting good practice
Reducing adverse incidents and ensuring lessons are learned
Preventing poor performance and misconduct
Research Governance is for all those who:
Participate in research
Host research in their organisation
Fund research proposals or infrastructure
Manage research
Undertake research
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Declaration of Helsinki
The Declaration of Helsinki is a landmark international agreement adopted in 1964 by the World Medical
Association recommending ethical standards in medical research. A fifth revision of this short document,
approved in 2000, addresses issues raised as a result of rapid expansion of biomedical research.
The key points of the Declaration of Helsinki are:
It is the duty of the physician to protect the life, health, privacy and dignity of the human subject.
Medical research involving human subjects must conform to generally accepted scientific
principles.
Effects on the environment and welfare of animals used for research must be considered.
Each experimental procedure should be fully described in a protocol and be considered by an
ethical review committee.
The research protocol should contain a statement of the ethical aspects
Medical research should be conducted by scientifically qualified personnel and supervised by a
clinically competent medical person.
Predictable risks and burdens should be weighed against foreseeable benefits for the subjects
and others.
Physicians should cease any investigations if the risks outweigh the potential benefits.
The importance of the objective should outweigh the risks and burden to the subject, especially
in healthy volunteer studies.
Medical research is only justified if there is reasonable likelihood that a population will be
benefited.
The subjects must be volunteers and fully informed participants.
The right of research subjects to safeguard their physical and mental integrity and privacy must
be respected.
Each potential subject must be adequately informed of and their freely given consent obtained
in writing.
Subjects in a dependant relationship with the research should be consented by an independent
physician.
For legally incompetent subjects, the investigator must obtain consent from a legally authorised
representative.
Where the legally incompetent subject is able to give assent to decisions about participation in
research, that assent should be obtained in addition to consent.
If research is intended on subjects who cannot consent, it must be justified to, and approved by,
the ethics committee.
Results of all trials conducted according to these principles should be accurately published and
made available.
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European Directive on Good Clinical Practice in Clinical Trials
The EU Directive of 2001 aims to harmonise and streamline clinical trials procedures throughout the
member states and to support GCP with a legislative framework. It relates to all intervention trials, both
academic and commercial.
The Directive relates to all trials involving medicinal products, and encompasses all personnel involved
with the clinical trial procedure.
The EU Directive was adopted by all Member States in February 2001 and was implemented in the UK in
May 2004 with the Medicines for Human Use (Clinical Trials) Act 2004 and subsequent Statutory
Instrument Amendments.
Guidance provided by the EU directive:
Properly obtained and documented informed consent must be obtained.
Adherence to data protection directive 95/46/EEC is required.
Indemnity and insurance to cover liability of Investigator and Sponsor is required.
Subjects must be given a contact point from where further information can be obtained.
Extensive details relating to the conduct of clinical trials using those unable to give consent.
A single ethics committee opinion is required for multi-centre studies.
60 days maximum is allowed for an ethics committee to provide an opinion (35 days for an
amendment).
Extensions to these approval times apply when studies involve gene/cell therapies.
A database with details of European trials and adverse events will be set up.
Adverse event reporting to be standardised.
GCP inspections to become mandatory.
Controls to be placed on the manufacture and labelling of investigational products.
Studies can be stopped in the event of sponsor and/or investigator non-compliance.
The EU Directive is applicable to all centres performing interventionist research trials. These include
academic institutions and those trial units supported by charities.
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Good Clinical Practice
Until 1997, there were several documents relating to good clinical practice (GCP). In 1997 an
international committee for the harmonization of good clinical practice (ICH-GCP) was formed to
produce a standard agreed by the European Union, Japan and the United States.
These guidelines were implemented in the participating countries, and had the advantage of facilitating
mutual acceptance of data by the regulatory authorities of those countries.
The first principle of the ICH-GCP guidelines is that:
“Clinical trials should be conducted in accordance with the ethical principles
that have their origin in the declaration of Helsinki and are consistent with GCP
and the applicable regulatory requirements.”
The ICH-GCP guidelines are very comprehensive and list responsibilities for all involved in research
activity. It includes specific sections listing responsibilities of ethics committees, Investigators and
Sponsors. There are also sections detailing the format of trial protocols, investigator brochures and
essential documents required for clinical trials.
The ICH-GCP guidelines were an attempt to unify GCP standards, but they were only ever guidelines, and
lacked the legal status needed to ensure that everyone adopted them. Although most sponsor
companies adopted the guidelines from the outset, there were some that did not. In particular,
academic research units found the workload cost implications were too great to implement the
guidelines. Also, some ethics committees were reluctant to adhere to the extra requirements that ICH-
GCP guidelines made of them, since they were not legally obliged to do so.
However, in 2000, the European Union issued a clinical trials directive that requires the adherence to the
principles of GCP. The EU Directive was transposed into UK law through the Medicines for Human Use
(Clinical Trials Act) Regulations, 2004.
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The Principles of ICH-GCP
1. Clinical trials shall be conducted in accordance with the ethical principles that have their origin in
the Declaration of Helsinki, and that are consistent with good clinical practice and the
requirements of the UK Regulations of Medicines for Human Use (Clinical Trials).
2. Before the trial is initiated, foreseeable risks and inconveniences have been weighed against the
anticipated benefit for the individual trial participant and other present and future patients. A
trial should be initiated and continued only if the anticipated benefits justify the risks.
3. The rights, safety, and well being of the trial subjects are the most important considerations and
shall prevail over interests of science and society.
4. The available non-clinical and clinical information on an investigational medicinal product shall
be adequate to support the clinical trial.
5. Clinical trials shall be scientifically sound, and described in a clear, detailed protocol.
6. A trial shall be conducted in compliance with the protocol that has a favourable opinion from an
ethics committee.
7. The medical care given to, and medical decisions made on behalf of, subjects shall always be the
responsibility of an appropriately qualified doctor or, when appropriate, of a qualified dentist.
8. Each individual involved in conducting a trial shall be qualified by education, training, and
experience to perform his or her respective task(s).
9. Subject to the other provisions relating to consent, freely given informed consent shall be
obtained from every subject prior to clinical trial participation.
10. All clinical trial information shall be recorded, handled, and stored in a way that allows its
accurate reporting, interpretation and verification.
11. The confidentiality of records that could identify subjects shall be protected, respecting the
privacy and confidentiality rules in accordance with the requirements of the Data Protection Act
1998 and the law relating to confidentiality.
12. Investigational medicinal products used in the trial should be manufactured, handled and stored
in accordance with the principles and guidelines of good manufacturing practice (GMP). They
should be used in accordance with the approved protocol.
13. Systems with procedures that assure the quality of every aspect of the trial shall be
implemented.
Although the law only applies to CTIMP studies, the principles of ICH-GCP should be applied to all
clinical research studies (CTIMP and non-CTIMP). All research should be conducted to the highest
standard whether governed by the law, or not.
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Health Research Authority & Ethics http://www.dh.gov.uk/health/2011/12/creation-hra
The Health Research Authority (HRA) is a Special Health Authority (SpHA), completing one of the key
commitments made by the Government in the Plan for Growth towards rationalising and improving
health research regulation. Its central purpose is to protect and promote the interests of patients and
the public in health research. The HRA will co-operate with others to combine and streamline the current
approval system and promote consistent, proportionate standards for compliance and inspection. The
purpose of this is for the HRA to reduce the regulatory burden on research-active businesses, universities
and the NHS, and improve the efficiency and robustness of decisions about research projects.
In its initial form as a SpHA, the HRA has the National Research Ethics Service (NRES) at its core and has
taken on the functions, which have been the responsibility of the National Patient Safety Agency. In due
course, it will perform the Secretary of State’s function of approving the processing of patient
information for medical research.
Ethics
Research Ethics Committees (RECs) are the committees convened to provide independent advice to
participants, researchers, funders, sponsors, employers, care organisations and professionals on the
extent to which proposals for research studies comply with recognised ethical standards.
The purpose of a REC in reviewing the proposed study is to protect the dignity, rights, safety and well-
being of all actual or potential research participants. It shares this role and responsibility with others,
as described in the Research Governance Framework.
Ethical advice from the appropriate NHS REC is required for any research proposal involving:
Patients and users of the NHS. This includes all potential research participants recruited by
virtue of the patient or user’s past or present treatment by, or use of, the NHS. It includes NHS
patients treated under contracts with private sector institutions.
Individuals identified as potential research participants because of their status as relatives or
carers of patients and users of the NHS, as defined above.
Access to data, organs or other bodily material of past and present NHS patients.
Foetal material and IVF involving NHS patients.
The recently dead in NHS premises.
The use of, or potential access to, NHS premises or facilities.
NHS staff – recruited as research participants by virtue of their professional role.
23
Roles & Responsibilities of Researchers and Organisations
Review of research - An independent expert review of protocols is required. - A separate ethical review of the study is required. - All data must be available to inspection and auditing bodies from both internal and external
organisations. - The protocol must not change without formal agreement from those who gave appropriate
permission for the study. Funder of research - Ensures quality and value for money, based on research costs and any care or treatment costs and
makes arrangements for independent expert review. - Ensures funding is conditional on identifying a sponsor (usually a university or NHS Trust). - Provides assistance to any enquiry, audit or investigation of the funded work. Sponsor All clinical trials and studies: - Responsible for ensuring expert scientific and ethics reviews are carried out. - Puts in place arrangements to adhere to GCP (if no other person is specified) and ensures
arrangements are in place to be alerted to significant developments. - Takes appropriate urgent safety measures (with investigator). - Ensures arrangements are in place for compensation (indemnity/insurance arrangements). - Keeps records of all adverse events reported by investigators. - Ensures the Research Ethics Committee is notified when the trial has ended. Clinical Trials involving investigational medicinal products (CTIMP): - Ensures the EudraCT (European Clinical Trials Database) Number is obtained. - Competent Authority Authorisation is obtained (Chief Investigator). - Pharmacovigilance reporting and time frames are adhered to. - EudraCT and the Competent Authority are notified when trial has ended.
24
Chief Investigator - Is responsible for the design, management and reporting of the study for all sites. - Is responsible for ensuring that each investigator is aware of their legal duties and obligations. - Is responsible for ensuring the protocol is approved by relevant bodies, any pre-conditions are acted
upon, and that research follows the agreed protocol except in the case of urgent safety measures. - Undertakes duties delegated by the sponsor (usually working in conjunction with a clinical research
organisation CRO if it is a pharmaceutically funded trial). - Publishes the clinical study results as soon as possible following study completion. In a multi-centre
study, the chief investigator must ensure that the data from one centre is not published before the publication of the whole study without his/her consent, and must obtain Sponsor approval prior to publication.
Principal Investigator It is the responsibility of the PI to conduct the study according to the protocol and to ensure that he/she has the necessary patient population available to conduct the study within the period defined in the study protocol. The investigator also holds additional responsibilities: - To ensure that the study is performed in accordance with the International Good Clinical Practice
standards (ICH-GCP) and conforms with the principles of the Declaration of Helsinki (revised version 1996), all local laws and regulations concerning clinical studies.
- To submit the protocol, patient information sheet and consent form for local Research Management & Governance approval (R&D approval).
- To ensure that all staff involved in the study have a full understanding of the protocol and its requirements, and that their roles are documented on a study delegation log.
- To confirm subject eligibility according to the inclusion/exclusion criteria stated in the protocol. - To obtain and record subject consent. - To withdraw a subject from the clinical trial for any reason should this be thought to be in their best
interests. - To perform protocol directed medical care including assessment, examination and prescription of
study and support medication. - To ensure subject anonymity is maintained. - To ensure the completeness and accuracy of case report forms. - To agree to allow the monitor/auditor/inspector to have access to any or all of the study materials
needed for source data verification and proper review of study progress. - To report all safety events: SAEs, SARs, SUSARs as outlined in the protocol, including prompt
reporting to Sponsor to ensure further communication with MHRA/REC if applicable within the statutory timelines.
- To retain all essential documents as per NHS and Trust guidelines (usually a minimum of five years following the end of a study, at least two years after the approval of a marketing application, for a new drug, or longer if required by the regulator requirements).
- To comply with the study sponsor and regulatory authority requirements regarding the auditing of the study.
25
Co-investigator (Medical) The co-investigator is responsible for medical care of patients participating in research studies, working under the supervision of the principle investigator. The co-investigator is usually delegated the following responsibilities: - To ensure that the study is performed in accordance with ICH-GCP and conforms with the principles
of the Declaration of Helsinki (revised version 1996), all local laws and regulations concerning clinical studies.
- To confirm subject eligibility according to the inclusion/exclusion criteria stated in the protocol. - To obtain and record patient consent. - To withdraw a subject from the clinical trial for any reason should this be thought to be in their best
interest. - To perform protocol directed medical care including assessment, examination and prescription of
study and support medication. - To ensure subject anonymity is maintained. - To ensure the completeness and accuracy of case report forms. - To agree to allow the monitor/auditor/inspector to have access to any or all of the study materials
needed for source data verification and review of study progress. - To retain all essential documents as per NHS and Trust guidelines (usually a minimum of five years
following the end of a study, at least two years after the approval of a marketing application, for a new drug, or longer if required by the regulator requirements).
- To comply with the study sponsor and regulatory authority requirements regarding the auditing of the study.
Research Nurse/AHP/Midwife/Clinical Trials Officer/Practitioner The research nurse/AHP/Midwife/CTO is delegated responsibilities by the PI, these may include: - Preparing and submitting local regulatory approval applications. - Ensuring that they have attended an initiation meeting and received any appropriate training prior to
the trial commencement. - Co-ordinating the clinical trial in terms of patient screening, recruitment, entry into the trial via
randomisation if applicable and subsequent patient visits. - Checking patient eligibility according to the inclusion/exclusion criteria stated in the protocol in
collaboration with medical staff. - Collaborating with clinicians to assess patients and making treatment decisions according protocol. - Delivery of investigational agents/treatments and protocol directed care. - Handling, spinning, labelling, storage and shipping of blood and urine pharmacokinetic samples. - Ensuring that source documentation is a true reflection of decisions and actions taken for each
individual patient. - Completion of case report forms and ensuring relevant follow up data is collected (eg QoL data). - Monitoring and reporting all safety events: SAEs, SARs, SUSARs as outlined in the protocol, including
prompt reporting to Sponsor to ensure further communication with MHRA/REC if applicable within the statutory timelines.
- Liaising with the study sponsor regarding the conduct of the trial. - Educating patients/subjects and dissemination of trial related information to staff.
26
Data Managers/Research Assistants Non Clinical research support staff work closely with the research nurses and other members of the clinical team to ensure accurate and appropriate data collection. Their delegated responsibilities may include: - Ensuring that they have attended a site initiation meeting and received any appropriate training
necessary in order to conduct the trial safely and efficiently. - Entering subjects into clinical trials, utilising appropriate randomisation procedures when necessary. - Completing case report forms and other research records. - Ensuring that all data is available for monitoring visits. - Assisting with or completing submissions to Ethics/Research and Development. - Archiving all clinical trial related documents according to regulatory requirements. - Shipping blood and urine pharmacokinetic samples. - Entering data and updating fields/information within databases. Clinical Trials Pharmacist As the number and variety of trials continues to increase it is vital that there is a good communication between the sponsor, the research team and the trials pharmacist. This will ensure issues are raised and resolved at an early stage, allowing the trial to run smoothly and effectively. Early input from pharmacy in the planning of a clinical trial enables early recognition of potential pharmaceutical issues; pharmacy should be given a copy of the protocol at the earliest opportunity. The Clinical Trials Pharmacist will review: - The design of prescriptions so the correct trial supplies are ensured. - How the blinding of trial medication is to be achieved and maintained. - The requirement for documentation and record keeping. - Labelling requirements. - Drug receipt, delivery, reordering and stock checks. - The mechanism for continuation of supplies, if appropriate, once the trial period has finished. - Storage conditions for the trial medication. - Size of packaging, which has implications for storage space. - For parenterally administered products there may be a requirement for aseptic preparation. Organisations providing care - Must ensure the sponsor has assumed responsibility, research has been reviewed by appropriate
bodies, and that an authorised person has given written permission on behalf of the care organisation for the research to begin.
- Must arrange for researchers not employed by any NHS organisation to hold an NHS honorary contract.
- Must ensure adverse incidents are reported.
27
Substantial Protocol Amendments
Substantial amendments for MHRA approval:
During the conduct of a study it may be necessary to make changes to the study protocol. These may be
due to changes to the protocol, trial arrangements, the IMP and its manufacture, or if new data becomes
available that may affect the risks/benefits of the study or affect the safety of the subject.
The Sponsor is directly responsible for the processing of any amendments. At site the PI may carry out
urgent safety measures, such as temporarily halting the trial where subjects may be at risk, without prior
authorisation from the Sponsor. However this should be reported to the MHRA and Ethics Committee.
For all other substantial amendments, MHRA authorisation must be sought by the Sponsor before the
amendment is implemented.
All amendments should be processed using an Amendment Worksheet for version control purposes. All
amendments should also be recorded on an Amendment Log. These documents should be filed within
the Site File.
Guidance on what may be considered a substantial amendment is listed below:
Amendments related to the protocol
Purpose of trial
Design of trial
Informed consent
Recruitment procedure
Measures of efficacy
Schedule of samples
Addition or deletion of tests or measures
Number of participants
Age range of participants
Inclusion criteria
Exclusion criteria
Safety monitoring
Duration of exposure to the investigational medicinal product(s) (IMP)
Change of physiology of the IMP(s)
Change of comparator
Statistical analysis
28
Amendments related to the trial arrangements
Change of the principal investigator or addition of new ones (this means the lead investigator in each centre)
Change of the coordinating investigator
Change of the trial site or addition of new sites
Change of sponsor or legal representative
Change of the CRO assigned significant tasks
Change of the definition of the end of the trial
Amendments related to the IMP
Addition to stability data/change of expiry date
Change of formulation
Additional toxicology data
Change to route of synthesis
Manufacturer(s) of active substance
Manufacturing process of the active substance
Specifications of active substance
Manufacture of the medicinal product
Specification of the medicinal product
Specification of excipients where these may affect product performance
Shelf-life including after first opening and reconstitution
Major change to the formulation
Storage conditions
Test procedures of active substance
Test procedures of the medicinal product
Test procedures of non-pharmacopoeial excipients
29
Changes to clinical trial and human experience data where this is relevant to the ongoing trials (ie altered risk:benefit assessment) for example concerning:
Safety related to a clinical trial or human experience with the IMP
Results of new clinical pharmacology tests
New interpretation of existing clinical pharmacology tests
Results of new clinical trials
New interpretation of existing clinical trial data
New data from human experience with the investigational medicinal product
New interpretation of existing data from human experience with the investigational medicinal product
30
Non-substantial amendments
Non-substantial amendments do not have to be reported to the MHRA, but should be recorded
and be available upon request for inspection centrally and at the trial site. This would include
minor changes such as a change of telephone number.
Changes to non-clinical pharmacology and toxicology data where this is relevant to the ongoing trials (i.e. altered risk:benefit assessment. For example concerning:
Results of new pharmacology tests
New interpretation of existing pharmacology tests
Result of new toxicity tests
New interpretation of existing toxicity tests
Results of new interaction studies
31
Safety
Pharmacovigilance - “the recording and reporting of adverse events and reactions to medicinal products being used in a clinical trial”.
Throughout the duration of a clinical trial, data is collected to monitor the effects of the study and any
interventions on the participants, to ensure their safety and it is important to report any effects to
protect patients during the study. This information is collected and reviewed to assess the risk:benefit
ratio of any new treatments, or practices, used in a study and once it becomes standard care. For
example, the information leaflet that accompanies any medicines (giving information about the
medication and any possible side effects) has been produced from the safety information gathered
during and after the licensing of the drug.
Effects of study medication or interventions are recorded in the following categories:
Adverse Event (AE) - any untoward medical occurrence in a patient or clinical investigation subject administered a
pharmaceutical product and which does not necessarily have a causal relationship with this treatment
- protocol will specify whether it should be recorded on the CRF or not
Serious Adverse Event (SAE) Adverse events that: - result in death - are life-threatening - require in-patient hospitalisation or prolongation of existing hospitalisation - result in persistent or significant disability or incapacity - are a congenital anomaly or birth defect following maternal or paternal exposure - an event specified in the protocol as needing to be reported as serious - should be reported by fax to the sponsor within 24 hr of knowledge of event
Serious Adverse Reaction (SAR) - an event that is classed as serious and is consistent with the information provided about the
Investigational Medicinal Product - must be recorded in the CRF and reported annually to ethics and regulatory authorities
Suspected Unexpected Serious Adverse Drug Reactions (SUSAR) - if the nature or severity or frequency or outcome of the event is not consistent with the IMP
information - reporting of SUSARS must be expedited to main REC and MHRA
32
Human Tissue Act
Taken from Human Tissue Authority website – www.hta.gov.uk:
The Human Tissue Authority is an independent watchdog that protects public
confidence by licensing and inspecting organisations that store and use tissue for
purposes such as:
teaching about or studying the human body
carrying out post-mortem examinations
using human tissue to treat patients
carrying out research on human tissue
displaying human bodies or tissue in public (eg in a museum).
The HT Authority provides advice and guidance about the Human Tissue Act and the
Quality and Safety Regulations, (note: ‘Human Tissue Act 2006’ in Scotland).
Consent is the most important principle of the HT Act. Consent must be given for
bodies, body parts, organs and tissue to be stored and to be used for specific purposes
as set out in the HT Act and Q&S Regulations. The key principle of the HT Act is that a
person has the right to be asked for consent before any part of their body is used for
particular purposes. This applies whether the tissue comes from a living or a dead
person.
The HT Act uses the term ‘appropriate consent’ and this refers to the person who may give their consent. This could be the person from whom tissue is being taken, or if they are dead, by someone close to them, like a family member. For consent to be valid it must be given voluntarily and by a person who has the ability to make an informed decision. The person giving consent must also have the best information given to them so that they can make their decision. A person can also withdraw their consent at any time. An HTA licence is granted to an organisation if it shows it will comply with certain essential standards set down by the HTA. Organisations are inspected to check that they maintain good standards and follow appropriate procedures. Each licensed organisation has to nominate a person (Designated Individual) who will supervise the activities being carried out.
The Human Tissue Authority is funded by Department of Health and accountable to the
Secretary of State for Health.
33
Data Protection
Anyone processing personal data must comply with the eight enforceable principles of good practice.
They say that data must be:
Fairly and lawfully processed.
Processed for limited purposes.
Adequate, relevant and not excessive.
Accurate.
Not kept longer than necessary.
Process in accordance with the subject’s rights.
Secure.
Not transferred to countries without adequate protection.
Personal data covers both facts and opinions about the individual. It also includes information regarding
the intentions of the data controller towards the individual, although in some limited circumstances
exemptions will apply. With processing , the definition is far wider than before. For example, it
incorporates the concepts of obtaining, holding and disclosing.
The nature of research means that there is a large amount of paper and electronic data held about
research subjects.
All staff involved in research has a responsibility to their research subjects and their employer regarding
data protection.
All subject data should be stored in a secure room.
All subject data must be locked away if unattended.
No one should access subject data unless authorised to do so by research personnel and/or data
protection officer.
Subject confidentiality should be maintained by use of initials/numbers of on research material.
Electronic data must be password protected. In accordance with the Computer Security Policy.
Personal data that has the potential to identify research subjects should be kept in a secure
place.
Any concerns relating to data protection issues must be discussed with the departmental data protection
officer.
All staff should be stored in accordance with local NHS Trust policy.
34
Informed Consent
Within the context of clinical trials, valid informed consent may be regarded as:
The process by which a subject voluntarily confirms his/her willingness to participate in a particular
clinical trial, after having been informed of all aspects of the trial that are relevant to the subject’s
decision to participate.
When
It is morally and professionally unacceptable to perform any research related procedure on someone
without first obtaining their fully (valid) informed consent. The issue of valid informed consent has
prompted great discussion and thought, and really is a key issue in clinical research.
How
Informed consent should be obtained from subjects prior to any research related procedure being
performed. Consent is a continuous process not a one off event. Amendments or safety updates to a
study protocol and PIL will require re-consent of the patient/subject. Verbal consent during a study and
attendance at scheduled visits implies continued consent.
A designated Research Ethics Committee must have approved the consent process and
documentation for a particular study.
Informed consent form must be up to date and revised if new information becomes available
(must be re-approved by ethics committee if changed).
No coercion of subjects to participate.
Language of informed consent should be understandable and not cause subject to waive or
appear to waive or release investigator, institution or sponsor from responsibilities.
Inform subject of important information, including risks and side effects.
Language should be as non-technical as possible.
Allow subject time to review information before signing.
Allow time to answer questions and review issues raised by subject.
Consent form to be signed and dated by subject and person obtaining consent.
Subject must keep signed copy of consent.
Subject’s legal rights must be maintained.
It is essential to remember that even once a subject has signed an informed consent form, they can
withdraw from the trial at any time. It is the duty of the Investigator to reiterate this and reassure them
that they will not compromise their future medical care if they decide to withdraw.
35
Who
The issue of who should take consent has been debated at length. The guidance of the key GCP
documents, although helpful, is not clear.
The Declaration of Helsinki states: In any research on human beings, each potential subject must be
adequately informed of the aims, methods, anticipated benefits and potential hazards of the study and
the discomfort it may entail. He or she should be informed that they are at liberty to abstain from
participation in the study at any time. The Physician should then obtain the subjects freely given
informed consent, preferably in writing.
The EC guidelines state: The information to the patient should be given in oral and written form wherever
possible... and ... subjects must be allowed sufficient time to decide whether or not they wish to
participate.
It is widely acknowledged that other research personnel play a major role in the study team and are
often considered more approachable than the investigator. To this end, it would be foolish to exclude
them from the informed consent procedure/process. Although other research personnel may take part
in the consent process (explaining procedures, answering questions etc), responsibility for enrolling the
subject should lie with the investigator.
The investigator should ensure that subjects have fully understood what they are consenting to and sign
and date the consent form accordingly. Any research personnel involved in giving information during the
informed consent procedure should also sign the informed consent form.
This approach meets the criteria of the 3 key documents, and adheres to the Declaration of Helsinki. The
argument put forward by some, that the declaration is an old, almost obsolete document, is easily
refuted by the fact that it has had 5 separate reviews, (most recently 2000) and the informed consent
clause has not been changed and as such is considered appropriate.
36
STANDARD OPERATING PROCEDURES (SOPs) – Log
SOP Number SOP Title Review and understood
(date & initials)
37
SOP Number SOP Title Review and understood
(date & initials)
38
CLINICAL RESEARCH NURSE INDUCTION PROGRAMME
This Induction Pack forms part of the Clinical Research Nurse Induction Programme and includes
guidance to ensure that you and your line manager can:
Plan a comprehensive induction programme,
Gain an understanding of the core skills and knowledge needed to work in research;
Review the competencies and complete the Clinical Research Nurse Competency Tool, to set
learning objectives and identify training opportunities.
As a Clinical Research Nurse you will be providing specialist care that will have a potential benefit to your
patients as well as a benefit to future patients. The role of a Clinical Research Nurse is diverse, covers
many specialties and is increasingly becoming recognised as a specialty in its own right. It can be a
challenging role but is an opportunity to use the skills you have gained in clinical practice, combined with
new research skills that you will acquire that will establish your career as a Clinical Research Nurse.
You will be responsible for ensuring that your clinical trials are completed according to the study
protocol, that you perform any tasks which are delegated to you and that you have sufficient experience
and training to complete these tasks.
The most important elements of your role will be to provide a high standard of care and ensure patient
safety and to collect good quality data. The safety of your patients remains as important as it would in
a non-research role and poor data quality can affect the quality of the entire study.
This induction Pack is designed to give you the information you need at the outset. It aims to be a
comprehensive resource which you can refer back to throughout your career. It will form a foundation
to your learning and give you the opportunity to reflect upon this and signpost you to external resources
of further information, as your knowledge increases.
Training
In order to achieve your goals of patient safety and data quality and to adhere to legislative
requirements and research governance guidelines you will be required to complete Good Clinical
Practice (GCP) training. GCP training is mandatory for anyone working in clinical research. If you have
not completed GCP training before this is something that you will need to undertake as a priority during
the first month in post. GCP training can be undertaken as an online course or a full day classroom-
based course (NIHR Introduction to GCP) available several times per year within the Trust, University of
Leeds and through WYCLRN. Both ways have pros and cons but you may find it helpful to complete an
online course (which usually takes 3-4 hours) as soon as you can, followed by a full day course within the
first six months in post.
West Yorkshire CLRN offer a programme of training courses for clinical research nurses who are new to
research. This consists of 3 separate full day courses:
39
Introduction to GCP
Informed Consent
Introduction to Clinical Research
Details of these courses funded by the WYCLRN can be found on their website:
www.crncc.nihr.ac.uk/about us/ccrn/west yorks/news/training
The National Cancer Research Network has a training curriculum which can be viewed on
http://ncrndev.org.uk/index.php?option=com_content&task=view&id=142&Itemid=282 and can
sometimes be accessed by non-oncology researchers.
To record your professional development and to support the duties you are undertaking within your
studies it will be useful to set up a Training Folder (recommended inserts can be found in Appendix II).
This will demonstrate the experience you gain and training you complete as you progress through your
career. This should include a research CV (see appendix III) as well as copies of your GCP Certificate and
Informed Consent certificates as well as a copy of your job description.
Equipment
The equipment and resources that you will need to work in research will vary depending on the type of
studies you are involved in and whether or not research is new to your area or already established.
However, here is a suggestion of what you may find useful:
Desk, chair, PC, telephone
Fax machine (or access to a secure one)
Diary
Files to store any paper based data
Notebook and other general stationery items
Lockable filing cabinet(s)
Access to or use of:
Centrifuge (with training on safe use of this equipment)
Fridge
Freezer
Lab space
Photocopier
It is imperative that wherever possible research nurses or AHPs do not work in isolation. If you are a
lone worker in a particular area, please seek support and guidance from other experienced research
colleagues in other specialties. The R&D department and the Lead Nurse at WYCLRN can offer further
information.
40
Induction
It is important that you meet with your Line Manager to discuss the scope of your role, your previous
experience and ensure your Induction Programme covers all aspects of your role. Your Induction
Programme should include the following:
Familiarisation with working areas and induction into the building(s) as appropriate
Fire and evacuation procedures (attend Trust mandatory Fire Awareness Training)
Trust induction programme if new to Trust
ID badge and access procurement
Absence policy and arranging of annual leave
Clear understanding of line management and reporting
Information gathering around specialty area of practice, advice on key learning and sources of
appropriate information/courses
Allocation of a mentor or buddy for supervision and guidance
Familiarisation with data protection legislation and institutional policies
Internal governance procedures and quality assurance
Understanding the roles of RECs and R&D, and the statutory legislation for research governance
Understanding of research methods
How to describe randomisation and equipoise to potential subjects
Other trial related procedures, clinical and non-clinical
Introduction to multi-disciplinary team and attendance at MDT meetings where appropriate
Shadowing colleagues in clinical areas and for peer learning re research trial conduct
Introduction to blood sampling handling, processing, shipment
Dry ice handling and legislation/guidance
Familiarisation with departmental SOPs
Introduction to electronic information management systems
Participate in a monitoring visit
Pathway Co-ordinators (oncology)
Introduction to key staff:
Relevant consultants and wider medical team
Matron (or appropriate AHP line manager)
Directorate manager/faculty or R&D lead at University
R&D lead for specialty
Business Manager
Nursing and other local research colleagues
Outpatient or other patient areas to be utilised when conducting research
Administrative team and or wider research support staff as appropriate/available to your area
Example Induction Programme
Mon Tues Wed Thurs Fri
Week 1 Corporate Induction
– full day
Introduction to
Research Team
Local induction with
line manager
Meeting with PI
Meet with O/P
Clinic Sister
Visit by study
monitor
Meet with Lead
Nurse WYCLRN
Spend time with
Clinical Trials
Pharmacist
Study training with
research nurse
Week 2 Shadow Research
Nurse in clinic
NIHR Introduction to
GCP training
Attend new patient
clinic – OPD
Meet with CNS –
am
Shadow Research
Nurse in clinic
Attend Clinical
Research Forum –
12pm
Week 3 Lab training
Visit R&D Dept Attend Informed
Consent Training
Shadow Research
Nurse in clinic
Attend Inpatient
Service Team
Meeting
Week 4 Attend Directorate
Sisters meeting
Study training with
research nurse
SOP training with
line manager
Line Management Induction Programme Sign Off
Local Induction completed
Date:
Month 1 Induction Programme confirmed*
Date:
Competency Tool (Induction) reviewed and objectives set
Date:
Competency Tool (6 months) reviewed and objectives set
Date:
Competency Tool (12 months) reviewed and objectives set
Date:
Signature: Date: ______________________________
(Line Manager)
Signature: Date: ______________________________
(Research Nurse)
*It is your responsibility as well as your manager’s to ensure that you have a comprehensive Induction
Programme for the first month in post. This will be defined by the department you are based in and your
previous experience and therefore will need to be developed as part of your review.
43
Trial Design
Phases of Clinical Trials
Early Phase/Phase I Trials Phase 1 trials are the first test of a drug in humans; this typically involves a small number of participants in a gradual step wise approach, entering patients into dose cohorts, with careful assessment and evaluation before increasing the dose in further subjects. The main aim of such studies is to establish the safety profile, drug metabolism, disposition and tolerability in human subjects, building on existing preclinical data.
Phase II Trials Phase 2 trials aim to provide further safety information, adverse event management and information on drug activity (efficacy). These trials are normally used to determine dose regimens and obtain further safety data in a larger number of patients.
Phase III Trials Phase 3 trials are usually large scale comparative studies to look at the risks, benefits and side effects of a drug compared to or in combination with other drugs or placebo.
Phase IV Trials Phase 4 trials take place once the drug has been shown to be effective and has been granted a licence. These trials aim to find out how well the drug works when used more widely than in clinical trials, the long term risks and benefits and gain more information on the possible side effects and safety of the drug.
44
Clinical Trials Flow Chart
Team Review Feasibility assessment by team members
↓
Peer Review Written peer review to go with ethics submission (this will have been
done internally for commercially sponsored studies)
↓
Costing Resources, time, labs, tests etc
↓
Clinical Trial Review Process Obtain feedback from relevant staff and departments on their ability to
meet the requirements of the protocol
↓
ARSAC/IRMER Administration of Radioactive Substances Advisory Committee Ionising Radiation (Medical Exposure)Regulations
↓
EudraCT number Unique number issued or each trial from a database held by the
European Medicines Agency
↓
CTA Clinical trial agreement from the competent authority
(In the UK this is the MHRA)
↓
NHS Directorate or University Faculty Signoff
↓
IRAS process
↓
CSP Local R&D approval
45
Case Report Form Completion
A CRF is a record of all the data and other information on each subject required by the research protocol. The
ICH-GCP guidelines include strict guidance relating to CRF completion, as they are the official documentation
of the trial for the authorities. The CRFs, along with source documentation are closely examined in the event
of audit and inspection.
The CRF should collect necessary information about:
The enrolled subject.
Administration of the study drug or intervention.
Study specific procedures.
The outcome of any assessments.
Details of any adverse events, serious adverse events and SUSARs.
Only those personnel identified by the principal investigator should complete CRFs. These can include:
Co-investigators
Clinical trial practitioners
Research nurses/AHP
Anyone completing a CRF should have completed the signature delegation log in the Investigator file, and
provided a signed and dated copy of their CV.
CRFs should be completed as soon as possible after the associated visit/patient assessment to ensure that the
information is up to date and accurate. Before any monitoring or audit visits, it is essential to ensure that
CRFs are as up to date as possible.
There are guidelines to CRF completion with each study protocol. Some general points are given here for
reference.
Paper CRF
Always use a black ball point pen to complete paper CRFs.
If the CRF is on carbonless duplication paper, ensure that an appropriate separator is inserted.
Never leave blank spaces. If a section cannot be completed write, as appropriate, not known, not
certain, test not done.
46
All entries must be legible:
o Cross out incorrect entry with a single line, so that the original entry is still legible
o Enter the correct data
o Initial and data correction
o If it is not obvious, then give an explanation for alterations
The CRF for each patient MUST be signed off by the principle investigator to indicate that they believe
that they are complete and correct.
Electronic CRF
Adequate online training with the system to be used is required and will be facilitated by the study
sponsor.
A password will be issued to each individual authorised to access the system to enter data and should
be kept safe and never shared with others.
Data should be entered as soon as possible after the subjects scheduled visit.
Corrections and query resolution is auditable through the electronic system.
Provision is required at site to facilitate monitoring visits. And access to the electronic system.
Computers should not be left unattended with patient data on screen even though anonymised.
Adherence to the relevant data protection legislation is mandatory.
CRF completion is one of the most important roles of the clinical trials co-ordinator, as it is the only source of
data that will be received by the sponsor company. Therefore, accurate and thorough completion is essential.
Source documentation
Many items of data generated during routine and study related care episodes constitute source
documentation. For example, blood results, radiology reports, pharmacy prescriptions, letters in medical
notes, hand written notes in the patients record all constitute primary source data.
The development of study related source data sheets to capture relevant data items at designated study visit
time-points are helpful in ensuring that items are not overlooked or missed in error and can significantly
improve data quality overall. Such source sheets then also become primary source data and should be
retained with the subject’s medical notes for monitoring and data verification. If source data sheets are
created they need to be version controlled and signed and data on completion of primary data entry.
47
Essential Documents for the Conduct of a Clinical Trial
A Trial Master File (TMF) should be established before the start of a study. The TMF is a filing system, rather than a single file, that includes essential documents as defined by ICH-GCP that demonstrate the entire conduct of the study from beginning to end. Before the Clinical Phase of the Trial Commences During this planning stage the following documents should be generated and should be on file before the trial formally starts
Title of Document Purpose Located in Files of Investigator/ Institution
Sponsor
Investigator’s brochure To document that relevant and current scientific information about the investigational product has been provided to the investigator
X X
Signed protocol, amendments, sample case report forms
To document investigator and sponsor agreement to the protocol/amendment(s) and CRF
X X
Information given to trial subject: X X
Consent form (including all applicable translations)
Any other written information
Advertisement for subject recruitment
To document the informed consent To document that subjects will be given appropriate written information (content and wording) to support their ability to give fully informed consent To document that recruitment measures are appropriate and not coercive
X
X
X
Financial aspects of the trial To document the financial agreement between the investigator/institution and the sponsor for the trial
X X
Insurance statement (where required) To document that compensation to subject(s) for trial-related injury will be available
X X
Signed agreement between involved parties:
Investigator/institution and sponsor
Investigator/institution and CRO
Sponsor and CRO
Investigator/institution and authorities
To document agreements
X
X
X
X
X X X
Dated, documented approval/ favourable opinion of IRB/IEC:
To document that the trial has been subject to IRB/IEC review and given
X
X
48
Title of Document Purpose Located in Files of Investigator/ Institution
Sponsor
- protocol and any amendments - CRF (if applicable) - informed consent form(s) - any other written information to be
provided to the subject(s) - advertisement for subject recruitment
(if used) - subject compensation (if any) - any other documents given approval/
favourable opinion
approval/favourable opinion. To identify the version number and date of the document(s).
Institutional Review Board/ Independent Ethics Committee Composition
To document that the IRB/IEC is constituted in agreement with GCP
X X (where required)
Regulatory authorisation/approval/ notification of protocol (where required)
To document appropriate authorisation/approval/notification by the regulatory authority(ies) has been obtained prior to initiation of the trial in compliance with the applicable regulatory requirement(s)
X (where required)
X (where required)
Curriculum Vitae and/ or other relevant documents evidencing qualifications of investigator(s) and sub-investigator(s)
To document qualifications and eligibility to conduct trial and/or provide medical supervision of subjects
X X
Normal value(s) / range(s) for medical/laboratory/technical procedures and or tests included in the protocol
To document normal values and / or ranges of the tests results
X X
Medical laboratory/technical procedures/tests
- certification or - accreditation or - established quality control and/or
external quality assessment or - other validation
To document competence of facility to perform required test(s), and support reliability of results.
X (where
required)
X
Sample of labels attached to investigational product containers
To document compliance with applicable labelling regulations an appropriateness of instructions provided to the subjects.
X
Instructions for handling of investigational products and trial related materials
To document instructions needed to ensure proper storage, packaging, dispensing and disposition of investigational products and trial.
X X
49
Title of Document Purpose Located in Files of Investigator/ Institution
Sponsor
Shipping records for investigational products and trial related materials
To document shipment dates, batch numbers and method of shipment of investigational products and trial related materials. Allows tracking of product batch, review of shipping conditions, and accountability.
X X
Certificates of analysis of investigational products shipped
To document identity, purity and strength of investigational products to be used in the trial.
X
Decoding procedures for blinded trials To document how, in case of an emergency, identity of blinded investigational product can be revealed without breaking the blind for the remaining subjects’ treatment.
X
X(third party if
applicable)
Master randomisation list To document method for randomisation of trial population
X (third party if
applicable)
Pre-trial monitoring report To document that the site is suitable for the trial
X
Trial initiation monitoring report To document that trial procedures were reviewed with the investigator and the investigator’s trial staff
X X
50
During the Clinical Conduct of the Trial
Title of Document Purpose Located in files of Investigator/Institution
Sponsor
Investigators brochure updates To document that investigator is informed in a timely manner of relevant information as it becomes available
X X
Any revision to: - protocol/amendments and CRF - informed consent form - any other written information
provided to subjects - advertisement for subject
recruitment (if used)
To document revisions of these trial related documents that take effect during trial
X X
Dated, documented approval/favourable opinion of IRB/IEC of the following:
- protocol amendments - revision of - informed consent form - any other written information to
be provided to the subject - advertisement for subject
recruitment (if used) - any other documents given
approval/favourable opinion - continuing review of trial (where
required)
To document that the amendments and or revisions have been subject to IRB/IEC review and were given approval/favourable opinion. To identify the version number and date of the documents.
X X
Regulatory authorities authorisations/approvals/notifications where required for:
- protocol amendments and other documents
To document compliance with applicable regulatory requirements
X X (where required)
Curriculum vitae for new investigators and or sub-investigators
X X
Updates to normal values/ranges for medical/laboratory/technical procedures/tests included in the protocol
To document normal value and ranges that are revised during the trial
X X
Updates of medical/laboratory/technical procedures/tests
- certification or - accreditation or - established quality control and/or
external quality assessment or - other validation (where required)
To document that tests remain adequate throughout the trial period
X X (where required)
Documentation of investigational products and trial related materials shipment
X X
Certificates of analysis for new batches of X
51
Title of Document Purpose Located in files of Investigator/Institution
Sponsor
investigational products
Monitoring visit reports To document site visits by, and findings of, the monitor
X
Relevant communications other than site visits
- letters - meeting notes - notes of telephone calls
To document any agreements or significant discussion regarding trial administration, protocol violations, trial conduct, adverse event reporting
X X
Signed informed consent forms To document that consent is obtained in X accordance with GCP and protocol and dated prior to participation of each subject in trial. Also to document direct access permission.
X
Source documents To document the existence of the subject and X substantiate integrity of trial data collected. To include original documents related to the trial, to medical treatment, and history of subject.
X
Signed, dated and completed case report forms
To document that the investigator or authorised member of the investigator’s staff confirms the observations recorded.
X (copy) X (original)
Documentation of CRF corrections To document all changes/additions or corrections made to CRF after initial data were recorded
X (copy) X (original)
Notification by originating investigator to sponsor of serious adverse events and related reports
Notification by originating investigator to sponsor of series adverse events and related reports
X X
Notification by sponsor and/or investigator to regulatory authorities and IRB/IEC of unexpected serious adverse drug reactions and of other safety information
Notification by sponsor and/or investigator, where applicable, to regulatory authorities and IRB/IECs of unexpected serious adverse drug reactions and of other safety information.
X (where required)
X
Interim or annual reports to IRB/IEC and authorities
Interim or annual reports provided to IRB/IEC and to authorities
X X (where required)
Subject screening log To document identification of subjects who entered pre-trial screening
X X (where required)
Subject identification code list To document that investigator keeps a confidential list of names of all subjects allocated to trial numbers on enrolling in the trial. Allows investigator to reveal identity of any subject.
X
52
Title of Document Purpose Located in files of Investigator/Institution
Sponsor
Subject enrolment log To document chronological enrolment of subjects by trial number.
X
Investigational products accountability at the site
To document that investigational products have been used according to the protocol.
X X
Signature sheet To document signatures and initials of all persons authorised to make entries and/or corrections on CRFs
X X
Record of retained body fluids/tissue samples
To document location and identification of retained samples if assays need to be repeated.
X X
After completion or termination of the trial
Title of Document Purpose Located in files of
Investigator/Institution
Sponsor
Investigational products accountability at site
To document that the investigational products have been used according to the protocol. To document the final accounting of investigational products received at the site, dispensed to subjects, returned by the subjects, and returned to sponsor.
X X
Documentation of investigational product destruction
To document destruction of unused investigational products by sponsor or at site.
X (if destroyed at
site)
X
Completed subject identification code list To permit identification of all subjects enrolled in the trial in case follow up is required. List should be kept in a confidential manner and for agreed upon time.
X
Audit certificate (if available) To document that audit was performed.
X
Final trial close out monitoring report To document that all activities required for trial close out are completed, and copies of essential documents are held in the appropriate files.
X
Treatment allocation and decoding documentation
Returned to sponsor to document any decoding that may have occurred.
X
53
Title of Document Purpose Located in files of Investigator/Institution
Sponsor
Final report by investigator to IRB/IEC where required, and where applicable, to the regulatory authorities
To document completion of the trial. X
Clinical study report To document results and interpretation of trial.
X X
International Conference on Harmonisation of Technical Requirements for Registration of
Pharmaceuticals for Human Use (1996) ICH Harmonised Tripartite Guideline for Good Clinical Practice E6
(R1): http://www.ich.org/LOB/media/MEDIA482.pdfBBC
54
55
Clinical Research Nurse Competency Tool: Purpose of this document: This document has been developed to be a working tool for Clinical Research Nurses (CRNs) and their line managers to assess and review CRN competencies and is based directly on the Competency Framework for Clinical Research Nurses, A tool to promote patient safety and quality data (October 2011). Competencies are the essential skills and knowledge required by nurses to carry out their work in a safe and effective way. The competencies within this document have been identified as those unique to the role of a Clinical Research Nurse and are intended to provide clear guidance on the scope of this role and define the differences between bands 5 through to 8. How to use this document: During the first month in post the Clinical Research Nurse and their Line Manager should review the competencies together. The worksheets titled ‘Induction’ should be used to review the CRN competencies and should be used to identify personal objectives together with any training needs to form part of the CRN’s developmental plan. It is recommended that a review of the competencies is conducted at 6 months and again at 12 months using the ‘review worksheets’. The higher level of assessment target at 12 months demonstrates the level of knowledge and skills acquisition that should have occurred during the first 12 months in post.
What is a competency? The Competency Framework for Clinical Research Nurses defines competency as: “the ability to demonstrate the application of knowledge, understanding, practical and thinking skills to achieve effective performance in a professional or occupational role. This involves problem solving and
being sufficiently flexible to meet changing demands”. Further details on the use of competencies can be found in the Competency Framework.
56
The competencies
Competence 1
To demonstrate understanding of the background, political influence and strategy regarding clinical research in the UK
Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation
2.1 Understands the role and remit of research ethics committees in the UK
2.2 Contributes to the preparation of documentation and submissions of applications for ethical approval
Competence 3 To understand, apply and promote the principles and practice of
obtaining valid informed consent
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant-focused clinical research
4.1 Contributes to the development of safe clinical research
4.2 Contributes to efficient use of resources
4.3 Contributes to the delivery of clinical research
4.4 Contributes to the safe collection and storage of data and accurate completion of study documentation
57
Competence 1: To demonstrate understanding of the historical
background, political influence and strategy regarding clinical
research in the UK
Skills and behaviours Knowledge and understanding KSF
Understands the relevance of the historical development of clinical research to current research and policy.
Understands the current political context and relevant policy.
Champions the role of clinical research to the development of health, social care and the wealth of the nation.
Supporting and influencing the embedding of clinical research in NHS infrastructure / practice.
History of ethics related to clinical research [2-18].
Development of research ethics and governance [19-23].
Methodological developments in clinical research [24-27].
Political and strategic developments in clinical research [19, 28-34].
C1 C2 C3 C5 G5
Examples:
Band 5
Recognises the importance of acknowledging the historical context within which clinical research is undertaken.
Band 6 Articulates the significance of major historical events, publications and
policy developments in the evolution of clinical research, including political imperatives and government strategies.
Band 7 Demonstrates comprehensive knowledge and understanding of the historical context, political influence and strategic developments relating to the evolution of clinical research.
Band 8 Takes a leading role in supporting understanding of the historical and political context in which clinical research has developed and is currently being undertaken.
58
Competence 2: To work within the regulations framework
2.1 Understands the role and remit of research ethics committees in the UK
Skills and behaviours Knowledge and understanding KSF
Recognises the need to ensure
that appropriate ethical opinions and governance approvals are obtained before any research activities are undertaken.
Articulates understanding of regulatory requirements.
Undertakes relevant educational activities [35-40].
Structure and policy for the regulation of research [41-42].
Roles and responsibilities of RECs [19, 31-32, 43-47].
Structure and organisation of RECs and their membership [19, 41-44].
Structure and organisation of R&D Departments, their membership and their roles and responsibilities [31-32].
Processes for the submission of applications and their review [19, 29, 43-44, 46, 48-51].
Local policies and procedures related to ethical review and research governance [29, 31-32, 48].
Local and national policy developments [52-54].
Roles and responsibilities of investigators and other members of the research team [31-32].
Knowledge of procedures when breaches of protocol are identified or when fraud and misconduct is suspected [29, 39, 46, 48-49].
Actions required when processes to protect participant confidentiality are not followed.
C1 C2 C3 C5 G5
Examples:
Band 5 Understands the need for favourable ethical opinion and research and governance approval to be obtained before commencing research activities.
Has an awareness of the structure, roles and function of RECs and R&D Departments.
Knows how to raise concerns and report instances of protocol deviation.
Band 6 Contributes to the development of research protocols.
Has knowledge and understanding of structure, roles and function of RECs and R&D Departs.
Has Knowledge of local R&D policies and procedures.
Has familiarity with regulatory requirements.
Act as a knowledgeable resource and advisor to staff and researchers.
Contributes to supervision and meeting educational needs of staff.
Band 7 Provides comprehensive advice and guidance on matters relating to research ethics and governance.
Act as a resource to staff & contributes to the professional & educational development of staff.
Leads on the development and updating of local policies and procedures.
Leads on the professional and educational development of staff.
Band 8
Demonstrates leadership by:
Act as an expert resource to staff and researchers.
Leading on the professional and educational development of staff.
Ensuring appropriate reporting at the organisation executive board level.
Competence 2: To work within the regulations framework
2.2 Contributes to the preparation of submissions for regulatory reviews
59
Skills and behaviours Knowledge and understanding KSF
Aware of application processes and requirements for document management.
Leads or contributes to the preparation of paperwork and submission of applications.
REC and R&D application processes (IRAS) [19, 44, 55-57].
Other centralised permissions [58].
Key documentation required to support REC and R&D submissions [19, 56].
Protocol development.
Local review and reporting of research studies [59].
Clinical Research Agreements [60-61].
Risk assessment and feasibility.
Local and national policy developments.
Research sponsorship and researcher roles [31-32, 48, 56].
Professional responsibilities and potential for conflict with research role [62].
C1 C2 C3 C5 G5 HWB2
Examples:
Band 5 Articulates the importance of clear, complete and accurate submissions.
Familiar with application processes.
Band 6 Act as a knowledgeable resource for staff and researchers making applications for regulatory approvals.
Raises concerns and seeks to address incomplete, inaccurate or misleading documentation.
Contributes to supervision and meeting the educational needs of staff.
Band 7 Act as expert resource for staff and researchers preparing submissions for regulatory approval.
Prepares, or makes significant contribution to the preparation of applications for regulatory approval.
Contributes to the professional and educational development of staff and researchers.
Band 8 Ensuring that all processes, policies and standard operating procedures are in place.
Contributing to quality assurance.
Leading and taking responsibility for research in position of PI or CI.
60
Competence 3: To understand, apply and promote the principles and practice of
obtaining and maintaining valid informed consent
Skills and behaviours Knowledge and understanding KSF
Assures the provision of an environment conducive to obtaining valid informed consent.
Contributes to policy and practice development.
Aware of and is responsive to factors contributing to decision making during the consent process.
Assures patient safety by proactively managing any breaches of the informed consent process.
Principles of informed consent for participation in research [18, 63-65].
Roles of researchers, including CI and PI, in gaining and maintaining informed consent [31-32].
Role of research nurses [31-32, 40, 66-69].
Role of the REC [19, 42-43, 70-71].
Key information required in PIS and CF [19, 72-75].
Ongoing nature of informed consent.
Legal requirements related to gaining and maintaining valid informed consent, especially when participants lack capacity [76-80].
Local policies and procedures relating to gaining and maintaining valid informed consent.
C1 C2 C3 C4 C5 C6 HWB2 HWB3
Band 5 Effectively engages with research participants to ensure understanding of info about the
research.
Demonstrates an awareness of the factors contributing to a participant’s autonomous decision making during the consent process.
Complies with the informed consent processes as described in the approved protocol, including use of approved versions of PIS and CF.
Raises any concerns about the informed consent processes.
Recognises own learning needs and takes responsibility for maintaining up to date knowledge.
Provides evidence of training and understanding.
Recognises that informed consent is an ongoing process.
Band 6 Demonstrates a sound understanding of the need to identify issues which may impact on the process of gaining valid informed consent. Plans and implements actions to resolve these issues.
Receives informed consent when appropriate and as agreed in the approved protocol.
Supports participants through the consent process.
Band 7 Act as an expert resource to provide in-depth knowledge to acquire and maintain informed consent.
Contributes to the mentorship and monitoring of consent procedures.
Responsible for the reporting of poor consent processes that compromise patient safety and the study protocol.
Band 8 Demonstrates leadership by:
Attending and reporting to corporate boards regarding governance, policy and service development related to research.
Holding responsibility for the training and monitoring of correct consent processes in research.
Developing systems to ensure that correct procedures are adhered to.
Contributing to professional development and education of clinical research staff in the organisation.
Competence 4: To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research
61
4.1 Contribute to the development and facilitation of clinical research
Skills and behaviours Knowledge and understanding KSF
Has an understanding of the research designs and methodologies used in clinical research.
Understands the implications for practice of the regulatory and legal frameworks related to the planning, delivery and closure of clinical research studies.
Has a comprehensive knowledge and understanding of the regulatory and legal frameworks related to the planning, undertaking and closure of clinical research studies.
Encourage, appreciate and value the contribution of study participants in all areas of research activity.
The role of the National Institute of Health Research (NIHR) [48, 52, 81].
The need for Quality Assurance [82-83].
Phases of clinical research [84-85].
Different research study designs: including protocol design and development; sample size and power; inclusion and exclusion criteria; randomisation; blinding and unblinding [49, 81, 86-88].
Translational research [89-90].
Multi-centre studies.
Management processes from feasibility to closure [49, 91]
Pharmacovigilance [92-93].
Local, national and international dissemination of clinical research findings [94-97].
Relevant UK legislation [76, 98-103].
Professional codes of practice [62].
Roles of licensing authorities and the licensing of investigational products [29, 104-105].
Local requirements, policies and procedures.
C1 C2 C3 C5 G5
23
62
Examples:
Band 5 Consistently adheres to the study protocol design.
Raises concerns if design conflicts with regulatory frameworks and legal requirements or if research activities deviate from the study protocol.
Recognises own limitations and attends/completes relevant training (including GCP). Is supportive in the training of others.
Demonstrates an awareness of the need for patient and public involvement (PPI) in clinical research. This could include their involvement in any aspect of the research process.
Band 6 Act as a knowledgeable resource for staff, researchers, research participants and patients.
Contributes to the training and supervision of staff and researchers.
Contributes to the development of local policies related to all parts of the clinical research process.
Promotes and facilitates PPI in all aspects of clinical research.
Contributes to nurse led research.
Band 7 Act as an expert resource for staff, researchers, research participants and patients.
Demonstrates a detailed knowledge and understanding of different research designs and methodologies and the regulatory and legal frameworks related to clinical research studies.
Leads on the training and ensuring the appropriate supervision of staff.
Leading role in the development and updating of local policies and procedures.
Contributes to the development of national policies and procedures.
Leads in planning, conducting and supervising nurse led research.
Band 8 Demonstrates leadership by:
Playing an integral role in R&D for a, (locally, nationally and internationally).
Contributing strategically on all areas of clinical research.
Political astuteness.
Professional leadership.
Efficient and effective networking skills.
Further development of clinical research.
Prioritising competing needs.
Contributing to the professional development and education of clinical research staff and organisations.
Contributing to or leading clinical research.
25
63
4.2 Contribute to effective and efficient use of resources
Skills and behaviours Knowledge and understanding KSF
Has an awareness of the financial issues related to the planning and conducting of clinical research.
Recognises their role and contribution to the local and national strategic vision.
Funding of research studies [106].
Financial agreements [60-61].
Financial management during the course of a clinical research study [91].
Identification of costs [107].
Role of the research funder [31-32].
National and local research costing models.
Local employment policies and models of working.
C2 G5
Examples:
Band 5 Consistently operates within the financial constraints of the funding available for a clinical research study.
Alerts relevant personnel to potential escalating consumable and other costs associated with a clinical research study.
Is aware of different staff roles and responsibilities regarding resources.
Band 6 Contributes to the financial processes of planning, running and closing clinical research studies.
Band 7 Involved in the financial processes associated with coordinating research studies and grant applications.
Act as an expert resource for staff in relation to the financial management of clinical research studies.
Uses expert judgment in relation to competing demands for funding.
Involved in the management of staff as a resource.
Band 8 Demonstrates leadership by:
Building alliances and working partnerships.
Enhancing Institutional reputation
Skill mix review.
Contributing to the professional development of the workforce.
Contributing to the acquisition of grant income and identification of
other potential funding streams.
Cost recovery systems.
64
4.3 Facilitate the delivery of clinical research
Skills and behaviours Knowledge and understanding KSF
Contributes to the delivery of clinical research protocols as a member of the research team.
Understands the rationale behind adherence to ethical approved study protocols.
Demonstrates safe and effective care of patients and/or research participants in research.
Awareness of policies relating to Investigational Medicinal Products (IMP).
Recognise the importance of accurate and comprehensive source documentation.
Demonstrate a good understanding of GCP in relation to direct patient/participant care.
Local Medicines Policy.
Quality Assurance [82].
Standard Operating Procedures (SOPs) [108].
Relevant clinical skills in line with local procedures and national occupational standards [31-32].
Knowledge of research study protocol.
Processes for participant recruitment.
Risk Management.
Public involvement in research [87].
Importance of submitting recruitment figures to relevant bodies, including NIHR recruitment data [29, 52].
Local organisational policies and procedures.
C1 C2 C3 C5 Ik2 G5 G6
Band 5 Is able to correctly use and dispose of study supplies and equipment, in accordance with study protocol and relevant Standard Operating Procedures (SOPs).
Completes accurate paperwork associated with research study supplies.
Attends relevant training in relation to requirements of research study protocol.
Consistent application of relevant clinical and research skills.
Contributes to an active and effective research culture.
Band 6 Actively involved in the ordering of supplies, ensuring that resources (including staff and beds) are available for the effective conduct of the research study.
Ensures clear and accurate documentation is maintained on the arrival, use and disposal of research study supplies.
Advises staff and researchers, acting as a knowledgeable resource on matters relating to clinical practice and research, promoting an active and effective research culture.
Contributes to the development and training of staff and researchers.
Contributes to the development of SOPs.
Band 7 Takes a leading role in managing research studies.
Supports colleagues and researchers through the research study process, including clinical aspects associated with the research study.
Takes the lead on developing and updating SOPs.
Takes a leading role in activities of professional fora and networks.
Contribute to local recruitment strategies.
Band 8 Demonstrates leadership by: Having wider oversight and strategic vision.
Actively seeking to collaborate and share best practice to enhance delivery of clinical research.
Promoting effective recruitment strategies to increase recruitment in line with local/national targets.
4.4 Contribute to the safe collection and storage of data and accurate
completion of study documentation
65
Skills and behaviours Knowledge and understanding KSF
Undertakes, supervises and manages
the accurate and complete collection of data and insertion of data into Case Report Forms (CRFs) or other research storage formats.
Ensures the safe and secure storage of data.
Has a comprehensive understanding of the roles and responsibilities of key personnel within the clinical research environment.
Facilitating the monitoring process.
Ensures participant’s confidentiality.
Roles of those involved in all aspects of research [31-32, 66, 68, 109-111].
Data insertion techniques, including the use of electronic data entry.
Audio and other media as means of data.
Source document verification.
Fraud and misconduct [112].
Audit and monitoring of data [113].
The process of inspections [113].
Local and national policies and procedures relating to data collection and safe transfer [111, 114-120].
Local Caldicott guardian and local information governance policy [121].
Actions required when processes to protect confidentiality are not adhered to [116-117].
C1 C3 C5 Ik2 G5 HWB2
66
Examples:33 Band 5 Evidence of accurate and complete data collection and entry.
Adherence to requirements of ethically approved protocol.
Raises concerns if inaccurate or incomplete data entry is suspected.
Takes appropriate action in event of adverse events.
Contributes to the safe and secure storage of research data.
Consistently works within own role and adheres to the roles and responsibilities documentation.
Is aware of own role limitations and escalates up when necessary.
Understands the roles and responsibilities of others involved in clinical research.
Addresses non adherence to defined protocol/policies by timely and appropriate reporting.
Consistently adheres to requirements to protect confidentiality.
Raises concerns when processes to ensure confidentiality are not adhered to.
Band 6 Advises staff and researchers on data collection, data entry and safe data storage.
Responds to concerns if inaccurate or incomplete data entry is suspected.
Contributes to supervision and meeting the professional and educational needs of staff.
Contributes to study closure and archival preparation.
Act as a knowledgeable resource and contributes to the development and training of staff and researchers.
Contributes to the development and updating of local policies and procedures.
Band 7 Contributes to the development of local policies and procedures.
Ensures that local policies and procedures are followed by all members of the research team.
Contributes to the auditing and monitoring of research studies and responds to recommendations.
Takes an active lead in the setting up, coordination and management of clinical research studies.
Act as an expert resource for staff and researchers.
Takes an active role in developing and updating local and national policies and procedures.
Actively involved in local and national forums and networks related to clinical research and the nurse’s role in that clinical research.
Ensures that processes and procedures for ensuring participant confidentiality are developed and adhered to.
Band 8 Demonstrates leadership by:
Leading on the professional and educational development of staff.
Involvement in local implementation of national directives and policies.
Driving quality assurance measures and appropriate policies to enhance clinical research activity.
Involved in appropriate reporting at the organisational level.
67
Assessment Levels
Level 1 Is competent with assistance and supervision
Level 2 Is competent with supervision
Level 3 Is competent and autonomous with minimal assistance and supervision
Level 4 Supports, trains and supervises others
Band 5
Band 6
Band 7
Band 8
68
Induction Review Date
Competence 1 To demonstrate understanding of the background, political influence and strategy regarding clinical research in the UK
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
69
Induction Review Date
Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.1 Understands the role and remit of research ethics committees in the UK.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
70
Induction Review Date
Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.2 Contributes to the preparation of documentation and submissions of applications for ethical approval.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
71
Induction Review Date
Competence 3 To understand, apply and promote the principles and practice of obtaining valid informed consent.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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Induction Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.1 Contribute to the development of safe clinical research.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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Induction Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.2 Contributes to efficient use of resources.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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Induction Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.3 Contributes to the delivery of clinical research.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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Induction Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.4 Contributes to the safe collection and storage of data and accurate completion of study documentation.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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6 Month Review Date
Competence 1 To demonstrate understanding of the background, political influence and strategy regarding clinical research in the UK.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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6 Month Review Date
Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.1 Understands the role and remit of research ethics committees in the UK.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
6 Month Review Date
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Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.2 Contributes to the preparation of documentation and submissions of applications for ethical approval.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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6 Month Review Date
Competence 3 To understand, apply and promote the principles and practice of obtaining valid informed consent.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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6 Month Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.1 Contribute to the development of safe clinical research.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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6 Month Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.2 Contributes to efficient use of resources.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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6 Month Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participants focused clinical research. 4.3 Contributes to the delivery of clinical research.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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6 Month Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.4 Contributes to the safe collection and storage of data and accurate completion of study documentation.
Target Band 5 1 Band 7 2 Level achieved:
Band 6 1 Band 8 3
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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12 Month Review Date
Competence 1 To demonstrate understanding of the background, political influence and strategy regarding clinical research in the UK.
Target Band 5 2 Band 7 3 / 4 Level achieved:
Band 6 3 Band 8 4
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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12 Month Review Date
Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.1 Understands the role and remit of research ethics committees in the UK.
Target Band 5 2 Band 7 3 / 4 Level achieved:
Band 6 3 Band 8 4
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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12 Month Review Date
Competence 2 To work within, and adhere to, the requirements of research ethics, research governance and legislation. 2.2 Contributes to the preparation of documentation and submissions of applications for ethical approval.
Target Band 5 2 Band 7 3 / 4 Level achieved:
Band 6 3 Band 8 4
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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12 Month Review Date
Competence 3 To understand, apply and promote the principles and practice of obtaining valid informed consent.
Target Band 5 2 Band 7 3 / 4 Level achieved:
Band 6 3 Band 8 4
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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12 Month Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.1 Contribute to the development of safe clinical research.
Target Band 5 2 Band 7 3 / 4 Level achieved:
Band 6 3 Band 8 4
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
89
12 Month Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.2 Contributes to efficient use of resources.
Target Band 5 2 Band 7 3 / 4 Level achieved:
Band 6 3 Band 8 4
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
90
12 Month Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participants focused clinical research. 4.3 Contributes to the delivery of clinical research.
Target Band 5 2 Band 7 3 / 4 Level achieved:
Band 6 3 Band 8 4
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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12 Month Review Date
Competence 4 To apply professional knowledge and skills to facilitate efficient, safe and participant focused clinical research. 4.4 Contributes to the safe collection and storage of data and accurate completion of study documentation.
Target Band 5 2 Band 7 3 / 4 Level achieved:
Band 6 3 Band 8 4
Evidence at review:
Identified Objectives:
To be actioned by:
Training needs identified:
To be actioned by:
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▼ Appendix I - Research Professional Forum, Terms of Reference
Aims of the Research Practice Network
To bring together nurses and midwives in the Trust who have an interest in research To raise the profile of research nurses and midwives in the Trust To act as a forum to discuss the managerial needs of research nurses and midwives in the
Trust To support the professional development and educational needs of Trust nurses and
midwives involved in research To develop the research capability and capacity of research nurses and midwives in the Trust To act as a forum to share best practice To act as a forum to present existing research projects and to share ideas for future projects
to strengthen the research profile in nursing and midwifery research in the Trust To promote the dissemination and translation of research findings into practice, locally,
nationally and internationally
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Training folder sections
In order to demonstrate your ongoing professional development
and research experience, it is recommended that you maintain a
training folder. The following headings are recommended for use
to organise this document:
1. Name and Position, Copy of Job Description
2. Signed and Dated CV
3. List of Professional Associations
4. GCP Training Certificates and Research Specific
Competencies
5. Publications and Presentations
6. Continuing Education and Professional Development Log
7. Trust Mandatory Training
8. Professional and Higher Educational Certificates
9. Miscellaneous
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Appendix III - Research CV Template
SUBMISSION OF CURRICULUM VITAE (CV) TO RESEARCH ETHICS COMMITTEES AND NHS R&D OFFICES
Guidance for applicants
Your CV needs to demonstrate that you are qualified by education, training and experience to
conduct the research.
A standard template for an investigator CV is set out below. This template would be suitable for
submission of CVs by:
Chief Investigators (for submission with main REC application)
Local Principal Investigators (for submission with the Site-Specific Information Form to RECs and NHS R&D offices)
Academic supervisors (for submission with student applications).
The template is issued as guidance and is not intended to be prescriptive. Use of the template is not
a requirement for a valid application.
The NRES Standard Operating Procedures state that CVs should be a maximum of 2 pages. This is
also guidance and is not an absolute requirement.
It is important that experience relevant to the specific research project is fully summarised, but the
overall document should be kept concise. It is not necessary to provide a complete record of the
applicant’s professional and academic background. In particular, CVs should not include lengthy lists
of publications.
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This template is recommended by NRES and the NHS R&D Forum for applications both for ethical review and R&D approval.
CURRICULUM VITAE
Name:
Present appointment: (Job title, department, and organisation.)
Address: (Full work address.)
Telephone number: Email address:
Qualifications:
Professional registration: (Name of body, registration number and date of registration.)
Previous and other appointments: (Include previous appointments in the last 5 years and
other current appointments.)
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Research experience: (Summary of research experience, including the extent of your
involvement. Refer to any specific clinical or research experience relevant to the current
application.)
Research training: (Details of any relevant training in the design or conduct of research, for
example in the Clinical Trials Regulations, Good Clinical Practice, consent or other training
appropriate to non-clinical research. Give the date of the training.)
Relevant publications: (Give references to all publications in the last two years plus other
publications relevant to the current application.)
Signature: Date:
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GLOSSARY AE
Adverse Event
ABPI
Association of the British Pharmaceutical Industry
ARSAC Administration of Radioactive Substances Advisory Committee
CF Consent Form
CI Chief Investigator
Clinical Trial
A clinical trial is a research study designed to methodologically answer specific questions about novel therapies, treatment techniques or new ways of using known treatment. Clinical trials (also called medical research and research studies) are used to determine whether new drugs or treatments are both safe and effective. Carefully conducted clinical trials are the fastest and safest way to find treatments that work in people.
CRN Clinical Research Nurse
Clinical Trial Regulations
The Medicines for Human Use (Clinical Trials) Regulations 2004
Clinical Trial Authorisation
The authorisation from the MHRA as Competent Authority, in the UK to conduct a clinical trial of an investigational medicinal product (CTIMP).
Clinical Trial of an Investigational Medicinal Product (CTIMP)
Is any investigation in human subjects, other than non-investigational trial, intended to a) discover or verify the clinical, pharmacological or other pharmacodynamic effects of one or more medicinal products; b) to identify any adverse reactions to one or more such products or c) to study absorption, distribution, metabolism and excretion of one or more such products with the object of ascertaining the safety or efficacy of those products.
Cohort
In epidemiology, a group of individuals with some characteristics in common.
Community-based Clinical Trial
A method of providing experimental therapeutics prior to final approval for use in humans, this procedure is used with very sick individuals who have no other treatment options. Often approval is on a case-by-case basis.
Complementary and Alternative Therapy
Broad range of healing philosophies, approaches, and therapies that Western (conventional) medicine does not commonly use to promote well-being or treat health conditions.
Confidentiality Regarding Trial Participants
Refers to maintaining the confidentiality of trial participants including their personal identity and all personal medical information. The trial participants consent to the use of their records for data verification purposes should be obtained prior to the trial and assurance must be given that confidentiality will be maintained.
Contraindication A specific circumstance when the use of certain treatments could be harmful.
Control Group The standard by which experimental observations are evaluated. In many clinical trials, one group of patients will be given an experimental drug or treatment, while the control group is given either a standard treatment for the illness or a placebo (See Placebo and Standard Treatment).
CRA Clinical Research Associate (Monitor)
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CRF Case Report Form
CRO Contract Research Organisation
CRUK Cancer Research UK
CTA Clinical Trials Authorisation
CTC Common Toxicity Criteria
DMC
Data Monitoring Committee
Data Safety and Monitoring Board (DSMB)
An independent committee composed of community representatives and clinical research experts that review data while a clinical trial is in progress to ensure that participants are not exposed to undue risk. A DSMB may recommend that a trial be stopped if there are safety concerns or if the trial objectives have been achieved.
Diagnostic Trials Refers to trials that are conducted to find better tests or procedures for diagnosing a particular disease or condition. Diagnostic trials usually include people who have signs or symptoms of the disease or illness being studied.
Dose-ranging Study A clinical trial in which two or more doses of an agent (such as a drug) are tested against each other to determine which dose works best and is least harmful.
Double-blind Study A clinical trial design in which neither the participating individuals nor the study staff knows which participants are receiving the experimental drug and which are receiving the placebo (or another therapy). Double-blind trials are thought to produce objective results, since the expectations of the doctor and the participants about the experimental drug do not affect the outcome (See Blind, Single-Blind Study and Placebo).
Drug-Drug Interaction
A modification of the effect of a drug when administered with another drug, the effect may be an increase or a decrease in the action of either substance, or it may be an adverse effect that is not normally associated with either drug.
ECMC Experimental Cancer Medicines Centre
Efficacy The maximum ability of a drug or treatment to produce a result regardless of dosage. A drug passes efficacy trials if it is effective at the dose tested and against the illness for which it is prescribed.
Eligibility Criteria Summary criteria for participant selected; includes inclusion and exclusion criteria (See Inclusion and Exclusion Criteria).
EMEA European Medicines Evaluation Agency
EORTC European Organisation for Research and Treatment of Cancer
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EU Directive Directive 2001/20 EC of the European Parliament and the Council of the European Union relating to the implementation of good clinical practice in the conduct of the clinical trials of medicinal products for human use.
EudraCT European Drug Regulation authorities in Clinical Trials
Expanded Access Refers to the distribution of experimental drugs to participants who are failing on currently available treatments for their condition and who are also unable to participate in ongoing clinical trials.
Food and Drug Administration (FDA)
The US Department of Health and Human Services agency responsible for ensuring the safety and effectiveness of all drugs, biologics, vaccines and medical devices, including those used in the diagnosis, treatment and prevention of HIV infection, AIDS and AIDS-related opportunistic infections. The FDA also works with the blood banking industry to safeguard the US national blood supply.
GCP Good Clinical Practice
GLP Good Laboratory Practice
GMP Health Research Authority
Good Manufacturing Practice The HRA works closely with the MHRA and NIHR creating a unified approval process and to promote proportionate standards for compliance and inspection within a consistent national system of research governance
Hypothesis A supposition or assumption advanced as a basis for reasoning or argument, or as a guide to experimental investigation.
Inclusion/Exclusion Criteria
The medical or social standards determining whether a person may or may not be allowed to enter a clinical trial, these criteria are based on such factors as age, gender, the type and stage of a disease, previous treatment history, and other medical conditions. It is important to note that inclusion and exclusion criteria are used to identify appropriate participants and keep them safe.
Informed Consent The process of learning the key facts about a clinical trial before deciding whether or not to participate. It is also a continuing process throughout the whole of the study to provide information to participants. To help someone decide whether or not to participate, the doctors and nurses involved in the trial explain the details of the study.
Informed Consent Document
A document that describes the rights of the study participants, and includes details about the study, such as its purpose, duration, required procedures and key contacts. Risks and potential benefits are explained in the informed consent document. The participant then decides whether or not to sign the document. Informed consent is not a contract and the participant may be withdrawn from the trial at any time.
ICH GCP International Conference on Harmonisation – Good Clinical Practice
ICR Institute of Clinical Research
Investigational Medicinal Product (IMP)
A pharmaceutical form of an active substance or placebo being tested, or to be tested, or used, or to be used, as a reference in a clinical trial, and includes a medicinal product which has a marketing authorisation but is, for the purposes of the trial:
a) Used to assembled (formulated or packaged) in a way different from the form of the product authorised under the authorisation;
b) Used for an indication not included in the summary of product characteristics under
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the authorisation for that product; c) Used to gain further information about the form of that product as authorised
under the authorisation.
Investigator’s Brochure (IB)
A document containing a summary of the clinical and non-clinical data relating to an investigational medicinal product which are relevant to the study of the product in human subjects.
IRAS
Integrated Research Application System
IRMER Ionising Radiation Medical Exposure Regulations
KSF Knowledge and Skills Framework Lead Site In the case of a multi-site study, the site for which the Chief Investigator is also the Principal
Investigator.
Medicines and Healthcare products Regulatory Agency (MHRA)
Is the competent authority for the UK in relation to the EU Directive and the Clinical Trials Regulations. MHRA (Devices) is the competent authority for the UK in relation to the Medical Devices Regulations 2002.
NHS National Health Service
NIGB National Information Governance Board
NIHR National Institute of Health Research
NIHR CSP NIHR Coordinated System for gaining NHS permission
National Research Ethics Centre
Directorate within the National Patient Safety Agency that provides help and leadership for RECs by co-ordinating the development of operational and infrastructure arrangements in support of their work. This includes implementing standards to ensure national consistency, providing training for REC members and Co-ordinators, identifying IT solutions for procedural management and establishing regional REC centres to manage RECs.
Open Label Trial A clinical trial in which doctors and participants know which drug or treatment is being administrated.
Peer Review Review of a clinical trial by experts chosen by the study sponsors. These experts review the trial for scientific merit, participant safety and ethical considerations.
PIS
Participant information sheet
PPI
Patient and public involvement
Pharmacokinetics The process of absorption, distribution, metabolism and excretion of a drug or vaccine.
Placebo A placebo is an inactive pill, liquid, or powder that has no treatment value. In clinical trials, experimental treatments are often compared with placebos to assess the treatments effectiveness.
Placebo Controlled Study
A method of investigation of drugs in which an inactive substance is given to one group of participants, while the drug that is being tested is given to another group. The results obtained in the two groups are then compared to see if the investigational treatment is
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more effective in treating the condition.
Principal Investigator (PI)
The investigator responsible for the research site where the study involves specified procedures requiring site-specific assessment. There should be one PI for each research site. In the case of a single-site study, the CI and the PI will normally be the same person.
Protocol A document that describes the objectives, design, methodology, statistical considerations (or other methods of data analysis) and organisation of a research study.
Quality of Life Trials Refers to trials that explore ways to improve comfort and quality of life for individual’s chronic illness.
Randomisation A method by which study participants are assigned to a treatment group. Randomisation minimises the differences among groups by equally distributing people among the trial arms.
Randomised Trial A study in which participants are randomly assigned to one of two or more treatment arms of a clinical trial.
R&D
Research and Development
REC
Research Ethics Committee
Serious Adverse Event (SAE)
Serious adverse event, an untoward occurrence that results in death, is life-threatening, requires hospitalisation or prolongation of existing hospitalisation, results in persistent or significant disability or incapacity or consists of a congenital anomaly or birth defect.
Single Blind A study in which one party, either the investigator or participant is unaware of what medication the participant is taking.
Site Specific Assessment (SSA)
An assessment of the suitability of the investigator, site and facilities made for any study with a Principal Investigator at each research site. The application for SSA should be made by the Principal Investigator using the Site-Specific Information (SSI) Form. In the case of a multi-site study, the outcome of the SSA should be notified to the main REC within 25 days.
SOP Standard Operating Procedure
Sponsor The person who takes on ultimate responsibility for the initiation, management and financing (or arranging the financing) of a clinical trial.
Standard Treatment A treatment currently approved, in wide use and considered to be effective in the treatment of a specific disease or condition.
Statistical significance
The probability that an event or difference occurred by chance or alone. In clinical trials, the level of statistical significance depends on the number of participants studied and the observations made, as well as the magnitude of differences observed.
Serious Adverse Reaction (SAR)
A serious adverse reaction in a CTIMP that results in death; is life-threatening; requires hospitalisation or prolongation of existing hospitalisation; results in persistent or significant disability or incapacity; or consists of a congenital anomaly or birth defect.
Suspected Unexpected Serious Adverse Reaction
A SUSAR is a CTIMP which is unexpected, meaning that its nature and severity are not consistent with the information about the medicinal product in question set out:
a) In the case of a product with a marketing authorisation, in the summary of product
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(SUSAR) characteristics for that product; b) In the case of any other investigational medicinal product, in the investigator’s
brochure relating to the trial in question.
TMF
Trial Master File
TSF Trial Site File
UKCRC United Kingdom Clinical Research Collaboration
Further resources:
NIHR Clinical Research Network
www.crncc.nihr.ac.uk/about_us
NIHR Clinical Research Portfolio
www.crncc.nihr.ac.uk/about_us/processes/portfolio
Search the NIHR portfolio database
www.crncc.nihr.ac.uk/about_us/processes/portfolio/p_search
Primary Care Research Network (PCRN)
www.crncc.nihr.ac.uk/about_us/pcrn
Mental Health Research Network:
www.mhrn.info/
Dementias and Neurodegenerative Diseases Research Network
www.crncc.nihr.ac.uk/about_us/dendron
Diabetes Research Network
www.crncc.nihr.ac.uk/about_us/drn
National Cancer Research Network
www.ncrn.org.uk/
Yorkshire Cancer Research Network
www.ycrn.org.uk
Yorkshire Stroke Network
yorkshire.uksrn.ac.uk
Yorkshire Cancer Network
www.yorkshire-cancer-net.org.uk
MHRA
www.mhra.gov.uk/index.htm
Clinical Trials Toolkit
www.ct-toolkit.ac.uk/
IRAS (Integrated Research Application System)
www.myresearchproject.org.uk
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Further Reading:
Plan for Growth
http://www.hm-treasury.gov.uk/ukecon_growth_index.htm
Liberating the NHS, Equity and Excellence
http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_117
353
The Strategy for UK Life Sciences
http://www.number10.gov.uk/wp-content/uploads/2011/12/8971-BIS-Life-Sciences-Prospectus-
BMK_Spreads.pdf
A "prospectus" entitled Investing in UK Health and Life Sciences
http://www.bis.gov.uk/assets/biscore/innovation/docs/s/11-1429-strategy-for-uk-life-sciences
The NHS Chief Executive's review: Innovation Health and Wealth - Accelerating Adoption and Diffusion
http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_131299
Developing the Role of the Clinical Academic Researcher in the Nursing, Midwifery and Allied Health
Professionals.
http://www.dh.gov.uk/en/Publicationsandstatistics/Publications/PublicationsPolicyAndGuidance/DH_132968
Competency Framework for Clinical Research Nurses
http://www.rcn.org.uk/development/researchanddevelopment/rs/publications_and_position_statements/co
mpetencies
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Useful Contacts
Research Support and Governance Office Bradford Institute for Health Research Temple Bank House Bradford Royal Infirmary Duckworth Lane Bradford BD9 6RJ T: (01274) 366808/ 364687/ 383418 E: [email protected]
The Research Governance Manager [email protected]
Angela Grange Lead Nurse Clinical Quality & Research/Trust Innovation Lead Bradford Institute for Health Research Temple Bank House Bradford Royal Infirmary Duckworth Lane Bradford BD9 6RJ T 01274 366809 M 07968 472411 E [email protected]
West Yorkshire Comprehensive Local Research Network 34 Hyde Terrace Leeds LS2 9LN Emma Giddings Lead Nurse T 0113 392 23765 M 07534 274555 E [email protected] Visit the WYCLRN Website: www.westyorks.crncc.nihr.ac.uk